• Investigative Magnetic Resonance Imaging
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• v.25 no.3
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• pp.172-182
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• 2021

Purpose: We evaluated the diagnostic performance of LI-RADS version 2018 using gadoxetic acid enhanced MRI for recurrent but untreated HCC in patients with prior history of HCC. Materials and Methods: We enrolled 50 consecutive patients who 1) prior history of treatment of HCC, 2) underwent liver surgery for radiological/clinical diagnosis of new HCC between 2013 to 2018, 3) had gadoxetic acid enhanced MRI within one month before surgery, and 4) did not have more than five HCCs or infiltrative tumors only. Two radiologists reviewed MRI and determined the presence of LR3, LR4 and LR5 observations except previously treated tumors based on LI-RADS version 2018 in consensus. We sub-classified LR4 into LR4m (LR4 with major features only) and LR4u (LR4 upgraded from LR3 by ancillary features). LR4u were further sub-classified into LR4ua (with arterial phase hyperenhancement) and LR4un (without arterial phase hyperenhancement). Results: PPV for LR5, LR4 and LR3 observations for recurrent HCC were 100%, 61.5% and 25.0%, respectively. 100% (3/3) of LR4m were HCC. However, PPV of LR4u was 56.5%. PPV of LR4ua and LR4un were 73.3% and 25.0%, respectively. Sensitivity of LR5 and LR5+LR4 observations as a diagnostic threshold were 32.1% and 89.3%, respectively. Sensitivity for LR5+LR4m+LR4ua observations for diagnosis of HCC were 83.7% and significantly superior to that of LR5 without significant deterioration of specificity (75.0%). Conclusion: In patients with prior history of HCC, LR4 observations by major features or with APHE may be regarded as recurrent HCCs given high sensitivity and comparable specificity/PPV to LR5 observations.

• Journal of the Korean Society of Radiology
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• v.17 no.1
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• pp.123-129
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• 2023

The purpose of this study was to analyze differences in imaging quality and dose difference between intra-venous (IV) and intra-arterial (IA) liver dynamic computed tomography (CT). Herein, retrospective, blinded analysis was conducted to analyze signal-to-noise and contrast-to-noise ratios in cases of patients who underwent IV or IA liver dynamic CT for transarterial chemoembolization (TACE), an interventional procedure for hepatocellular carcinoma. The dose length product (DLP) value stored in Picture Archive and Communication System (PACS) was used to calculate the effective dose and thereby compare differences in the dose between the two methods. The mean liver and spleen signal to noise ratio (SNR) was greater in IV-liver dynamic CT than in IA-liver dynamic CT; however, contrast to noise ratio (CNR) was higher in IA-liver dynamic CT than in IV-liver dynamic CT. However, there were no differences in DLP and effective dose between the two methods. In conclusion, our findings showed that IA-liver dynamic CT showed a similar effective dose and superior CNR compared with IV-liver dynamic CT. Further studies must analyze 3D angiography CT of the hepatic artery to clearly distinguish the feeding artery, which is the essential step in interventional procedures for hepatocellular carcinoma.

• Journal of Life Science
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• v.34 no.2
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• pp.94-104
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• 2024

β-Lapachone is a natural quinone compound originally obtained from the bark of the lapacho tree (Tabebuia vellanedae), which has been used in traditional medicine in several South and Central American countries for treating various diseases. Although β-lapachone has been reported to have potent anticancer activity in many types of cancer cells, its effect on the proliferation of hepatocellular carcinoma (HCC) cells is still unclear. Therefore, in this study, we investigated the effect of β-lapachone on the proliferation of human HCC Hep3B cells. According to our results, the decrease in cell viability of Hep3B cells caused by β-lapachone was closely related to the induction of apoptosis, which was confirmed through changes in nuclear morphology and flow cytometry. In addition, in Hep3B cells treated with β-lapachone, the expression of Bcl-2, an anti-apoptotic factor, was decreased, while the expression of Bax, an apoptosis inducer, was increased, and the activity of the caspase cascade was also increased. However, in the presence of a pan-caspase inhibitor, β-lapachone-induced apoptosis was weakened, indicating that the induction of apoptosis by β-lapachone was caspase-dependent. Moreover, β-lapachone treatment activated extracellular-regulated kinase (ERK) signaling while inhibiting activation of the phosphoinositide 3 kinase (PI3K)/Akt pathway. Furthermore, the effect of the ERK inhibitor on suppressing the induction of apoptosis by β-lapachone was minimal, and the PI3K inhibitor significantly increased β-lapachone-induced apoptosis. The findings from this study will contribute to a better understanding of the anticancer activity of β-lapachone in HCC cells.

• Korean Journal of Radiology
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• v.22 no.10
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• pp.1628-1639
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• 2021

Objective: Based on the Liver Imaging Reporting and Data System version 2018 (LI-RADS, v2018), this study aimed to analyze LR-5 diagnostic performance for hepatocellular carcinoma (HCC) when threshold growth as a major feature is replaced by a more HCC-specific ancillary feature, as well as the frequency of threshold growth in HCC and non-HCC malignancies and its association with tumor size. Materials and Methods: This retrospective study included treatment-naive patients who underwent gadoxetate disodium-enhanced MRIs for focal hepatic lesions and surgery between January 2009 and December 2016. The frequency of major and ancillary features was evaluated for HCC and non-HCC malignancies, and the LR-category was assessed. Ancillary features that were significantly more prevalent in HCC were then used to either replace threshold growth or were added as additional major features, and the diagnostic performance of the readjusted LR category was compared to the LI-RADS v2018. Results: A total of 1013 observations were analyzed. Unlike arterial phase hyperenhancement, washout, or enhancing capsule which were more prevalent in HCCs than in non-HCC malignancies (521/616 vs. 18/58, 489/616 vs. 19/58, and 181/616 vs. 5/58, respectively; p < 0.001), threshold growth was more prevalent in non-HCC malignancies than in HCCs (11/23 vs. 17/119; p < 0.001). The mean size of non-HCC malignancies showing threshold growth was significantly smaller than that of non-HCC malignancies without threshold growth (22.2 mm vs. 42.9 mm, p = 0.040). Similar results were found for HCCs; however, the difference was not significant (26.8 mm vs. 33.1 mm, p = 0.184). Additionally, Fat-in-nodule was more frequent in HCCs than in non-HCC malignancies (99/616 vs. 2/58, p = 0.010). When threshold growth and fat-in-nodule were considered as ancillary and major features, respectively, LR-5 sensitivity (73.2% vs. 73.9%, p = 0.289) and specificity (98.2% vs. 98.5%, p > 0.999) were comparable to the LI-RADS v2018. Conclusion: Threshold growth is not a significant diagnostic indicator of HCC and is more common in non-HCC malignancies. The diagnostic performance of LR-5 was comparable when threshold growth was recategorized as an ancillary feature and replaced by a more HCC-specific ancillary feature.

• 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.24 no.8
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• pp.761-771
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• 2023

Objective: To investigate the association among the electrode placement method, electrode type, and local tumor progression (LTP) following percutaneous radiofrequency ablation (RFA) for small hepatocellular carcinomas (HCCs) and to assess the risk factors for LTP. Materials and Methods: In this retrospective study, we enrolled 211 patients, including 150 males and 61 females, who had undergone ultrasound-guided RFA for a single HCC < 3 cm. Patients were divided into four combination groups of the electrode type and placement method: 1) tumor-puncturing with an internally cooled tip (ICT), 2) tumor-puncturing with an internally cooled wet tip (ICWT), 3) no-touch with ICT, and 4) no-touch with ICWT. Univariable and multivariable Cox proportional-hazards regression analyses were performed to evaluate the risk factors for LTP. The major RFA-related complications were assessed. Results: Overall, 83, 34, 80, and 14 patients were included in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. The cumulative LTP rates differed significantly among the four groups. Compared to tumor puncturing with ICT, tumor puncturing with ICWT was associated with a lower LTP risk (adjusted hazard ratio [aHR] = 0.11, 95% confidence interval [CI] = 0-0.88, P = 0.034). However, the cumulative LTP rate did not differ significantly between tumor-puncturing with ICT and no-touch RFA with ICT (aHR = 0.34, 95% CI = 0.03-1.62, P = 0.188) or ICWT (aHR = 0.28, 95% CI = 0-2.28, P = 0.294). An insufficient ablative margin was a risk factor for LTP (aHR = 6.13, 95% CI = 1.41-22.49, P = 0.019). The major complication rates were 1.2%, 0%, 2.5%, and 21.4% in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. Conclusion: ICWT was associated with a lower LTP rate compared to ICT when performing tumor-puncturing RFA. An insufficient ablation margin was a risk factor for LTP.

• Korean Journal of Radiology
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• v.22 no.12
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• pp.1974-1984
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• 2021

Objective: This study aimed to compare the efficacy between no-touch (NT) radiofrequency ablation (RFA) and conventional RFA using twin internally cooled wet (TICW) electrodes in the bipolar mode for the treatment of small hepatocellular carcinomas (HCC). Materials and Methods: In this single-center, two-arm, parallel-group, prospective randomized controlled study, we performed a 1:1 random allocation of eligible patients with HCCs to receive NT-RFA or conventional RFA between October 2016 and September 2018. The primary endpoint was the cumulative local tumor progression (LTP) rate after RFA. Secondary endpoints included technical conversion rates of NT-RFA, intrahepatic distance recurrence, extrahepatic metastasis, technical parameters, technical efficacy, and rates of complications. Cumulative LTP rates were analyzed using Kaplan-Meier analysis and the Cox proportional hazard regression model. Considering conversion cases from NT-RFA to conventional RFA, intention-to-treat and as-treated analyses were performed. Results: Enrolled patients were randomly assigned to the NT-RFA group (37 patients with 38 HCCs) or the conventional RFA group (36 patients with 38 HCCs). Among the NT-RFA group patients, conversion to conventional RFA occurred in four patients (10.8%, 4/37). According to intention-to-treat analysis, both 1- and 3-year cumulative LTP rates were 5.6%, in the NT-RFA group, and they were 11.8% and 21.3%, respectively, in the conventional RFA group (p = 0.073, log-rank). In the as-treated analysis, LTP rates at 1 year and 3 years were 0% and 0%, respectively, in the NT-RFA group sand 15.6% and 24.5%, respectively, in the conventional RFA group (p = 0.004, log-rank). In as-treated analysis using multivariable Cox regression analysis, RFA type was the only significant predictive factor for LTP (hazard ratio = 0.061 with conventional RFA as the reference, 95% confidence interval = 0.000-0.497; p = 0.004). There were no significant differences in the procedure characteristics between the two groups. No procedure-related deaths or major complications were observed. Conclusion: NT-RFA using TICW electrodes in bipolar mode demonstrated significantly lower cumulative LTP rates than conventional RFA for small HCCs, which warrants a larger study for further confirmation.

• Journal of the Korean Chemical Society
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• v.56 no.6
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• pp.679-691
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• 2012

New series of metal complexes of Co(II), Ni(II), Cu(II), Zn(II), Pd(II) and Pt(II) with 4-(p-chlorophenyl)-1-(pyridin-2-yl)thiosemicarbazide (HCPTS) have been synthesized and characterized by elemental analyses, magnetic moment, spectra (IR, UV-Vis, $^1H$ NMR, mass and ESR) and thermal studies. The IR data suggest different coordination modes for HCPTS which behaves as a monobasic bidentate with all metal ions except Cu(II) and Zn(II) which acts as a monobasic tridentate. Based on the electronic and magnetic studies, Co(II), Cu(II), Pd(II) and Pt(II) complexes have square - planner, Ni(II) has mixed stereochemistry (tetrahedral + square planar), while Zn(II) is tetrahedral. Molar conductance in DMF solution indicates the non-ionic nature of the complexes. The ESR spectra of solid copper(II) complex show $g_{\parallel}$ (2.2221) > $g_{\perp}$ (2.0899) > 2.0023 indicating square-planar structure and the presence of the unpaired electron in the $d_x2_{-y}2$ orbital with significant covalent bond character. The thermal stability and degradation kinetics of the ligand and its metal complexes were studied by TGA and DTA and the kinetic parameters were calculated using Coats-Redfern and Horowitz-Metzger methods. The complexes have more antibacterial activity against some bacteria than the free ligand. However, the ligand has high anticancer activities against HCT116 (human colon carcinoma cell line) and HEPG2 (human liver hepatocellular carcinoma cell line) compared with its complexes.

• Journal of the East Asian Society of Dietary Life
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• v.17 no.4
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• pp.563-570
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• 2007

This study was performed to observe the antioxidative effects, antimutagenic capacity, and cytotoxic activity of the 70% ethanol extract, and fractions, of Agaricus blazei Murill mycelium, using DPPH free radical scavenging ability, the Ames test, and SRB assay, respectively. Among the fractions, ethyl acetate showed the most effective antioxidative capacity according to the $RC_{50}$(73.6 $\mu$g/mL) of the scavenging effect on the DPPH radical. The inhibition rate of both the aqueous fraction and 70% ethanol extract(200 $\mu$g/plate) toward the Salmonella typhimurium TA100 strain was 94.6%, and it was 89.4% against the mutagenesis induced by MNNG(0.4 $\mu$g/plate). In addition, an identical concentration of the 70% ethanol extract in the TA98 strain, and the ethyl acetate fraction in the TA100 strain, showed inhibition rates of 80.3% and 76.9%, respectively, the highest activities against the mutagenesis induced by 4NQO(0.15 $\mu$g/plate). The cytotoxic effects of the 70% ethanol extract and its fractions increased with increasing sample concentration against human cervical adenocarcinoma(HeLa), human hepatocellular carcinoma(Hep3B), human breast adenocarcinoma(MCF-7), human stomach adenocarcinoma(AGS), and human lung carcinoma (A549). A 1 mg/mL concentration of the ethyl acetate fraction showed cytotoxicities of 77%, 83.8%, 82.1%, 83.1%, and 92.6% against HeLa, Hep3B, MCF-7, AGS and A549, respectively.

• Journal of Korean Neurosurgical Society
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• v.46 no.6
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• pp.538-544
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• 2009

Objective : Primary treatment of spinal metastasis has been external beam radiotherapy. Recent advance of technology enables radiosurgery to be extended to extracranial lesions. The purpose of this study was to determine the clinical effectiveness and safety of stereotactic radiosurgery using Cyberknife in spinal metastasis. Methods : From June, 2002 to December, 2007, 129 patients with 167 spinal metastases were treated with Cyberknife. Most of the patients (94%) presented with pain and nine patients suffered from motor deficits. Twelve patients were asymptomatic. Fifty-three patients (32%) had previous radiation therapy. Using Cyberknife, 16-39 Gy in 1-5 fractions were delivered to spinal metastatic lesions. Radiation dose was not different regarding the tumor pathology or tumor volume. Results : After six months follow-up, patient evaluation was possible in 108 lesions. Among them, significant pain relief was seen in 98 lesions (91%). Radiological data were obtained in 83 lesions. The mass size was decreased or stable in 75 lesions and increased in eight lesions. Radiological control failure cases were hepatocellular carcinoma (5 cases), lung cancer (1 case), breast cancer (1 case) and renal cell carcinoma (1 case). Treatment-related radiation injury was not detected. Conclusion : Cyberknife radiosurgery is clinically effective and safe for spinal metastases. It is true even in previously irradiated patients. Compared to conventional radiation therapy, Cyberknife shows higher pain control rate and its treatment process is more convenient for patients. Thus, it can be regarded as a primary treatment modality for spinal metastases.