• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.551-561
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• 2021

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.22 no.5
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• pp.207-220
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• 2021

This study aimed to evaluate the impact of education and counselling by nurses on anxiety, uncertainty, and pain in patients with benign uterine tumors. Electronic databases, including PubMed, OVID, CINAHL, Google Scholar, and Korean databases and were searched during January 2020. A total of 401 studies were identified of which 13 were suitable for meta-analysis. Cochrane's risk of bias tool and the R version 3.5.2 (Meta-analysis with R) program were used for analysis. The authors performed a meta-analysis of the 13 trials that met eligibility criteria. The findings in this study indicate that the effect size of nursing education for anxiety was Hedges' g=-0.89 (95% CI:-1.39 to -0.47), as indicated by a "large effect size" and the effect size of pain was Hedges' g=-0.49 (95% CI:-0.95 to -0.02) as indicated by a "moderate effect size". The effect size of uncertainty was Hedges' g=-1.38 (95% CI:-3.98 to 1.23), and it was not statistically significant. In the meta-subgroup analyses by approach intervention type, cognitive-behavioral programs, demonstration intervention, and relaxation therapy had a significant effect. The risk of publication bias was low. It may therefore be concluded that pre-operative education by nurses for patients with benign uterine tumors would affect their levels of anxiety, uncertainty, and pain.

• The Korea Journal of Herbology
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• v.28 no.2
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• pp.67-73
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• 2013

Objective : Lithospermum Erythrorhizon (LE) has been used as an anti-bacterial and anti-inflammatory agent. However, it is unclear that LE aqueous extract could show the anti-inflammatory effects in RAW 264.7cells. The purpose of this study was to investigate the anti-inflammatory effect of aqueous extract from LE on lipopolysaccharide (LPS) - induced inflammatory response. Methods : To measure out the cytotoxicity of LE, we performed the MTT assay. To evaluate the anti-inflammatory effects of LE, we examined the inflammatory mediators such as nitric oxide (NO), prostaglandin E2 ($PGE_2$) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-${\alpha}$, interleukin, (IL)-$1{\beta}$ and (IL)-6) on RAW 264.7 cells. We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-${\kappa}B$) activation by western blot. Results : Aqueous Extract from LE itself did not have any cytotoxic effect in RAW 264.7 cells. Aqueous extract from LE inhibited LPS-induced productions of inflammatory mediators such as NO, $PGE_2$, and pro-inflammatory cytokines including TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 in RAW 264.7cells. In addition, LE inhibited the phosphorylation of p38 kinases (p38), c-Jun $NH_2$-terminal kinase (JNK), and NF-${\kappa}B$ activation in RAW 264.7 cells. Conclusion : LE down-regulated LPS-induced production of inflammatory mediators through the inhibition of p38, JNK and NF-${\kappa}B$ activation. Taken together, these results could provide the evidence for the anti-inflammatory effects of LE. Therefore, LE may be a novel target in the management of inflammation and help to support a potential strategy for prevention and therapy of inflammatory diseases.

• Journal of Ginseng Research
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• v.46 no.1
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• pp.62-70
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• 2022

Background: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.1
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• pp.16-28
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• 2023

Lung adenocarcinoma accounts for about 40% of all lung cancers. With the recent development of gene profiling technology, studies on mutations in oncogenes and tumor suppressor genes, which are important for the development and growth of tumors, have been actively conducted. Companion diagnosis using next-generation sequencing helps improve survival with targeted therapy. In this study, formalin-fixed paraffin-embedded tissues of non-small cell lung cancer patients were subjected to hematoxylin and eosin staining for detecting genetic mutations that induce lung adenocarcinoma in Koreans. Immunohistochemical staining was also performed to accurately classify lung adenocarcinoma tissues. Based on the results, next-generation sequencing was applied to analyze the types and patterns of genetic mutations, and the association with smoking was established as the most representative cause of lung cancer. Results of next-generation sequencing analysis confirmed the single nucleotide variations, copy number variations, and gene rearrangements. In order to validate the reliability of next-generation sequencing, we additionally performed the existing genetic testing methods (polymerase chain reaction-epidermal growth factor receptor, immunohistochemistry-anaplastic lymphoma kinase (D5F3), and fluorescence in situ hybridiation-receptor tyrosine kinase 1 tests) to confirm the concordance rates with the next-generation sequencing test results. This study demonstrates that next-generation sequencing of lung adenocarcinoma patients simultaneously identifies mutation.

• Journal of the Korean Society of Radiology
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• v.17 no.7
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• pp.1091-1097
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• 2023

Bolus is used in radiation therapy to prescribe an even dose to the tumor when the skin surface is inclined or has irregularities. At this time, the dose to the skin surface increases. Due to the patient's unique body structure and irregular skin, voids may occur between the bolus and the skin, which may reduce the accuracy of treatment. Therefore, in this study, the existing bolus and the self-produced bolus through 3D printing were applied to the nasal area, and the difference between the surface dose after treatment plan and the dose directly measured with an Optically Stimulated luminescence(OSL) dosimeter was compared to the existing bolus. The bolus rate was 97%, PLA 100.33%, ePETELA 75A 100.53%, and ePETELA 85A 100.36%. It was confirmed that there was little error in the measurement values and treatment plan values for each material. In addition, compared to when applying a conventional bolus, a difference of -3% to +0.5% for a 3D printed bolus can be confirmed, so a customized bolus produced through 3D printing can complement the shortcomings of the existing bolus. It is believed that there will be.

• Korean Journal of Radiology
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• v.22 no.8
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• pp.1289-1299
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• 2021

Objective: We aimed to evaluate the usefulness of arterial subtraction images for predicting the viability of hepatocellular carcinoma (HCC) after locoregional therapy (LRT) using gadoxetic acid-enhanced MRI and the Liver Imaging Reporting and Data System treatment response (LR-TR) algorithm. Materials and Methods: This study included 90 patients (mean age ± standard deviation, 57 ± 9 years) who underwent liver transplantation or resection after LRT and had 73 viable and 32 nonviable HCCs. All patients underwent gadoxetic acid-enhanced MRI before surgery. Two radiologists assessed the presence of LR-TR features, including arterial phase hyperenhancement (APHE) and LR-TR categories (viable, nonviable, or equivocal), using ordinary arterial-phase and arterial subtraction images. The reference standard for tumor viability was surgical pathology. The sensitivity of APHE for diagnosing viable HCC was compared between ordinary arterial-phase and arterial subtraction images. The sensitivity and specificity of the LR-TR algorithm for diagnosing viable HCC was compared between the use of ordinary arterial-phase and the use of arterial subtraction images. Subgroup analysis was performed on lesions treated with transarterial chemoembolization (TACE) only. Results: The sensitivity of APHE for viable HCCs was higher for arterial subtraction images than ordinary arterial-phase images (71.2% vs. 47.9%; p < 0.001). LR-TR viable category with the use of arterial subtraction images compared with ordinary arterial-phase images showed a significant increase in sensitivity (76.7% [56/73] vs. 63.0% [46/73]; p = 0.002) without significant decrease in specificity (90.6% [29/32] vs. 93.8% [30/32]; p > 0.999). In a subgroup of 63 lesions treated with TACE only, the use of arterial subtraction images showed a significant increase in sensitivity (81.4% [35/43] vs. 67.4% [29/43]; p = 0.031) without significant decrease in specificity (85.0% [17/20] vs. 90.0% [18/20]; p > 0.999). Conclusion: Use of arterial subtraction images compared with ordinary arterial-phase images improved the sensitivity while maintaining specificity for diagnosing viable HCC after LRT using gadoxetic acid-enhanced MRI and the LR-TR algorithm.

• Korean Journal of Radiology
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• v.22 no.2
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• pp.159-167
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• 2021

Objective: The aim of this study was to compare the survival rates of Korean females aged 40 to 49 years with breast cancer detected by supplemental screening ultrasound (US) or screening mammography alone. Materials and Methods: This single-institution retrospective study included 240 patients with breast cancer (mean age, 45.1 ± 2.8 years) detected by US or mammography who had undergone breast surgery between 2003 and 2008. Medical records were reviewed for clinicopathologic characteristics and detection methods. Disease-free survival (DFS) and overall survival (OS) were compared between patients with breast cancer in the US and mammography groups using the log-rank test. Multivariable cox regression analysis was used to identify independent variables associated with DFS and OS. Results: Among the 240 cases of breast cancer, 43 were detected by supplemental screening US and 197 by screening mammography (mean follow-up: 7.4 years, 93.3% with dense breasts). There were 19 recurrences and 16 deaths, all occurring in the mammography group. While the US group did not differ from the mammography group in tumor stage, the patients in this group were more likely to undergo breast-conserving surgery and radiation therapy than the mammography group. The US group also showed better DFS (p = 0.016); however, OS did not differ between the two groups (p = 0.058). In the multivariable analysis, the US group showed a lower risk of recurrence (hazard ratio, 0.097; 95% confidence interval, 0.001-0.705) compared to the mammography group. Conclusion: Our study found that Korean females aged 40-49 years with US-detected breast cancer showed better DFS than those with mammography-detected breast cancer. However, there were no statistically significant differences in OS.

• Journal of the Korean Society of Radiology
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• v.83 no.2
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• pp.317-330
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• 2022

Purpose To evaluate the various factors that affect renal function following percutaneous radiofrequency ablation (RFA) therapy in patients with renal tumors. Materials and Methods Between 2010 and 2018, 91 patients diagnosed with renal tumors using ultrasonography and CT-guided RFA were enrolled. We retrospectively investigated the serum creatinine (SCr) level and estimated glomerular filtration rates immediately prior to RFA and during post-treatment follow-up. The patients were divided into two groups based on the degree of change in SCr level (0.3 mg/dL). Group comparisons were performed using univariable and multivariable logistic regression analyses to determine the factors impacting renal function. Results Impaired renal function was associated with solitary kidney, chronic kidney disease (CKD) over stage 3, and pyeloureteral injury. Sex, age, other cancers, tumor size, location, growth pattern, and proximity to the collecting system were not significantly associated with impaired renal function. There was a difference in the overall change over time between the association with and without solitary kidney, CKD stage 3, and pyeloureteral injury. Conclusion Among the medical conditions present prior to RFA, solitary kidney and CKD over stage 3 could be considered as risk factors for impaired renal function. Post-procedural pyeloureteral injury can also be considered a risk factor.

• Korean Journal of Radiology
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• v.24 no.6
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• pp.498-511
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• 2023

Objective: To evaluate the diagnostic performance of chest computed tomography (CT)-based qualitative and radiomics models for predicting residual axillary nodal metastasis after neoadjuvant chemotherapy (NAC) for patients with clinically node-positive breast cancer. Materials and Methods: This retrospective study included 226 women (mean age, 51.4 years) with clinically node-positive breast cancer treated with NAC followed by surgery between January 2015 and July 2021. Patients were randomly divided into the training and test sets (4:1 ratio). The following predictive models were built: a qualitative CT feature model using logistic regression based on qualitative imaging features of axillary nodes from the pooled data obtained using the visual interpretations of three radiologists; three radiomics models using radiomics features from three (intranodal, perinodal, and combined) different regions of interest (ROIs) delineated on pre-NAC CT and post-NAC CT using a gradient-boosting classifier; and fusion models integrating clinicopathologic factors with the qualitative CT feature model (referred to as clinical-qualitative CT feature models) or with the combined ROI radiomics model (referred to as clinical-radiomics models). The area under the curve (AUC) was used to assess and compare the model performance. Results: Clinical N stage, biological subtype, and primary tumor response indicated by imaging were associated with residual nodal metastasis during the multivariable analysis (all P < 0.05). The AUCs of the qualitative CT feature model and radiomics models (intranodal, perinodal, and combined ROI models) according to post-NAC CT were 0.642, 0.812, 0.762, and 0.832, respectively. The AUCs of the clinical-qualitative CT feature model and clinical-radiomics model according to post-NAC CT were 0.740 and 0.866, respectively. Conclusion: CT-based predictive models showed good diagnostic performance for predicting residual nodal metastasis after NAC. Quantitative radiomics analysis may provide a higher level of performance than qualitative CT features models. Larger multicenter studies should be conducted to confirm their performance.