• Biomolecules & Therapeutics
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• v.14 no.3
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• pp.148-151
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• 2006

We have previously reported that 2.4 kb of L-plastin promoter (LP) could regulate the expression of adenoviral vector (AV) exogenous genes in a tumor cell specific manner. In the present study, we tested if the replication competent AdLPE1A vector results in a direct cytotoxic effect in hepatocelluar carcinoma (HCC) cells. In vitro cytotoxicity tests were carried out with replication-competent (AdLPE1A) and -incompetent (AdLPCD) LP-driven vectors. AdLPE1A is an AV in which LP was inserted 5' to the E1A and E1B genes. The AdLPCD vector contains LP and the E. coli cytosine deaminase (CD) gene in transcription unit. Exposure of cells to AdLPE1A generated a significant cytotoxic effect as compared to the control. Almost 90% of the cell had manifested the characteristic cytopatic effect on day 9 after infection of cells with 10 MOI of AdLPE1A. On the other hand, almost 35% of the cells were left when the cells had been treated with 100 MOI of AdLPCD together with 5-FC on day 9 when compared with the cells which had never been exposed neither 5-FC nor AdLPCD. These results showed that the replication competent AdLPE1A vector could kill the HepG2 cells directly by the oncolytic effect of the virus. The replication competent AV vector carrying viral E1A generated greater cytotoxic effect than the replication incompetent AV, which contains the CD prodrug activation transcription unit without E1A, in HepG2 cells.

• Korean Journal of Radiology
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• v.23 no.6
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• pp.615-624
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• 2022

Objective: To compare the therapeutic outcomes of laparoscopic hepatic resection (LHR) and laparoscopic radiofrequency ablation (LRFA) for single subcapsular hepatocellular carcinoma (HCC). Materials and Methods: We screened 244 consecutive patients who had received either LHR or LRFA between January 2014 and December 2016. The feasibility of LRFA in patients who underwent LHR was retrospectively assessed by two interventional radiologists. Finally, 60 LRFA-feasible patients who had received LHR and 29 patients who had received LRFA as the first treatment for a solitary subcapsular HCC between 1 cm and 3 cm were finally included. We compared the therapeutic outcomes, including local tumor progression (LTP), recurrence-free survival (RFS), and overall survival (OS) between the two groups before and after propensity score (PS) matching. Multivariable Cox proportional hazard regression was also used to evaluate the difference in OS and RFS between the two groups for all 89 patients. Results: PS matching yielded 23 patients in each group. The cumulative LTP and OS rates were not significantly different between the LHR and LRFA groups after PS matching (p = 0.900 and 0.003, respectively). The 5-year LTP rates were 4.6% and 4.4%, respectively, and OS rates were 100% and 90.7%, respectively. The RFS rate was higher in LHR group without statistical significance (p = 0.070), with 5-year rates of 78.3% and 45.3%, respectively. OS was not significantly different between the LHR (reference) and LRFA groups in multivariable analyses, with a hazard ratio (HR) of 1.33 (95% confidence interval, 0.12-1.54) (p = 0.818). RFS was higher in LHR (reference) than in LRFA without statistical significance in multivariable analysis, with an HR of 2.01 (0.87-4.66) (p = 0.102). Conclusion: There was no significant difference in therapeutic outcomes between LHR and LRFA for single subcapsular HCCs measuring 1-3 cm. The difference in RFS should be further evaluated in a larger study.

• The Korean Journal of Nuclear Medicine
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• v.28 no.1
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• pp.62-68
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• 1994

This study was aimed to compare the density of the functional microcirculation of hepatocellular carcinoma (HCC) with normal liver and to investigate the effect of hepatic-arterial oily chemoembolization (HAE) by radionuclide examination. Methods : Eight patients with HCC proven by biopsy in five, and clinically and radiologically in three were included. The mixture of 2 cc normal saline with three to four mCi of $^{99m}Tc$-MAA was infused through a hepatic-arterial catheter for a minute. Dynamic images were obtained at a rate of 4 sec per frame for a minute, and static images and SPECT were followed. Results : In three patients who underwent hepatic arterial angiography (HAA) alone, radioactivity was markedly increased in tumors compared to the adjacent liver immediately after infusion of $^{99m}Tc$-MAA. The ratios of tumoral and extratumoral up-take (T/E ratio) were above 6.5 (range; $6.5{\sim}l9$, mean; 12.5). In four of the five patients who under-went superselective HAE, T/E ratio were remark-ably decreased ($0.5{\sim}1.3$). The areas of embolization were better delineated in radionuclide study than in postembolization HAA. In the other one who was considered to be embolized completely on HAA, strong radiouptake in the tumor was disclosed (T/E ratio; 7.0). Conclusions : Therefore hepatic-arterial flow study with radionuclide imaging using $^{99m}Tc$-MAA can be a valuable method to assess the accurate embolization effect in HCC.

• Journal of Digestive Cancer Research
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• v.5 no.1
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• pp.28-31
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• 2017

The number of laparosocpic liver resection performed every years has been increasing. There is a trend than more major hepatectomy and complex liver resection is being reported. However there has been a major obstacles in many centers because open liver resection is still considered as a gold standard and many surgeons are still getting used to the old method of liver resection. To start a new procedure, education and training is essential in order to achieve a good outcome without compromising the safety of the patients. A gradual progression is crucial in order to avoid dreadful complication. The development of the consensus meeting and difficulty score has facility the understanding of safe practice in the development of laparoscopic liver resection. In a long run, development of registry system will improve transparency and safety of this operation.

• Progress in Medical Physics
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• v.20 no.4
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• pp.235-243
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• 2009

The purpose of this experiment is to know the relation of the detection and characterization of liver's diseases as comparison of finding at MR imaging using a Ferucarbotran (SPIO) and Gd-EOB-DTPA (Primovist) agents in diffuse liver disease. A total of 50 patients (25 men and 25 women, mean age: 50 years) with liver diseases were investigated at 3.0T machine (GE, General Electric Medical System, Excite HD) "with 8 Ch body coil for comparison of diseases and contrast's uptake relation, which used the LAVA, MGRE." All images were performed on the same location with before and after Ferucarbotran and Gd-EOB-DTPA administrations (p<0.05). Contrast to noise ratio of Ferucarbotran and Gd-EOB-DTPA in the HCC were $3.08{\pm}0.12$ and $7.00{\pm}0.27$ with MGRE and LAVA pulse sequence, $3.62{\pm}0.13$ and $2.60{\pm}0.23$ in the hyper-plastic nodule, $1.70{\pm}0.09$ and $2.60{\pm}0.23$ in the meta, $2.12{\pm}0.28$ and $5.86{\pm}0.28$ in the FNH, $4.45{\pm}0.28$ and $1.73{\pm}0.02$ in the abscess and ANOVA test was used to evaluate the diagnostic performance of each disease (p<0.05). In conclusions, two techniques were well demonstrated with the relation of the detection and characterization of liver's diseases.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.1
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• pp.26-35
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• 2019

$^{188}Re$ is one of the most readily available generator derived and useful radionuclides for therapy emitting ${\beta}^-$ particles (2.12 MeV, 71.1% and 1.965 MeV, 25.6%) and imageable gammas (155 keV, 15.1%). The $^{188}W/^{188}Re$ generator is an ideal source for the long term (4-6 months) continuous availability of no carrier added (NCA) $^{188}Re$ suitable for the preparation of radiopharmaceuticals for radionuclide therapy. Rhenium-188 has been used for the preparation of therapeutic radiopharmaceuticals for the management of diseases such as bone metastasis, rheumatoid arthritis and primary cancers. Several early phase clinical studies using radiopharmaceuticals based on $^{188}Re$ -labeled phosphonates, antibodies, peptides, lipiodol and particulates have been reported. In this review, we addressed the current development status of $^{188}Re$ radiopharmaceuticals for liver cancer therapy and their applications.

• The Journal of Internal Korean Medicine
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• v.27 no.1
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• pp.138-148
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• 2006

Objectives: This study was designed to investigate the effects of Injinchunggan-tang(Yinchenqinggan-tang) on expression of angiogenic factors in HepG2 cells. Materials and Methods : The mRNA expression levels and protein secretion levels of angiogenic factors were measured using quantitative RT-PCR, Western blot and ELISA assay respectively in Injinchunggan-tang-treated and untreated HepG2 cells. Results : Injinchunggan-tang(Yinchenqinggan-tang) reduced mRNA expression levels and protein secretion levels of angiogenic factors, especially VEGF, bFGF and $TGF{\beta}1$ in HepG2 cells. Conclusion: Results indicate that Injinchunggan-tang (Yinchenqinggan-tang) inhibits expression of angiogenic factors in HepG2 cells. Further, results suggest that Injinchunggan-tang (Yinchenqinggan-tang) inhibits angiogenic effects in HCC.

• BMB Reports
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• v.55 no.9
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• pp.459-464
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• 2022

Various mechanisms have been suggested to explain the chemopreventive and tumor-inhibitory effects of melatonin. Despite the growing evidence supporting melatonin-induced mitochondrial dysfunction, it remains largely unknown how this phenomenon modulates metabolic reprogramming in cancer cells. The aim of our study was to identify the mechanism underlying the anti-proliferative and apoptotic effects of melatonin, which is known to inhibit glycolysis. We analyzed the time-dependent effects of melatonin on mitochondrial respiration and glycolysis in liver cancer cells. The results showed that from a cell bioenergetic point of view, melatonin caused an acute reduction in mitochondrial respiration, however, increased reactive oxygen species production, thereby inhibiting mTORC1 activity from an early stage post-treatment without affecting glycolysis. Nevertheless, administration of melatonin for a longer time reduced expression of c-Myc protein, thereby suppressing glycolysis via downregulation of HK2 and LDHA. The data presented herein suggest that melatonin suppresses mitochondrial respiration and glycolysis simultaneously in HCC cells, leading to anti-cancer effects. Thus, melatonin can be used as an adjuvant agent for therapy of liver cancer.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.3
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• pp.235-245
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• 2008

Purpose: The HSV1-tk gene has been extensively studied as a type of reporter gene. In hepatocellular carcinoma (HCC), only a small proportion of patients are eligible for surgical resection and there is limitation in palliative options. Therefore, there is a need for the development of new treatment modalities and gene therapy is a leading candidate. In the present study, we investigated the usefulness of substrate, 2'-fluoro-2'-deoxy-1-${\beta}$-D-arabino-furanosyi-5-[$^{124/125}I$]iodo- uracil ([$I^{124/125}I$]FIAU) as a non-invasive imaging agent for HSV1-tk gene therapy in hepatoma model using small animal PET. Material and Methods: With the Morris hepatoma MCA cell line and MCA-tk cell line which was transduced with the HSV1-tk gene, in vitro uptake and correlation study between [$^{125}I$]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [$^{124}I$]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. Results:, Specific accumulation of [[$^{125}I$]FIAU was observed in MCA-tk cells but uptake was low in MCA cells. Uptake in MCA-tk cells was 15 times higher than that of MCA cells at 480 min. [$^{125}I$]FIAU uptake was linearly correlated (R2 =0.964, p =0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [$^{125}I$]FIAU was mainly excreted via the renal system in the early phase. Ratios of MCA-tk tumor to blood acting were 10, 41, and 641 at 1 h, 4 h, and 24 h post-injection, respectively. The maximum ratio of MCA-tk to MCA tumor was 192.7 at 24 h. Ratios of MCA-tk tumor to liver were 13.8, 66.8, and 588.3 at 1 h, 4 h, and 24 h, respectively. On small animal PET, [$^{124}I$]FIAU accumulated in substantial higher levels in MCA-tk tumor and liver than MCA tumor. Conclusion: FIAU shows selective accumulation to HSV1-tk expressing hepatoma cell tumors with minimal uptake in normal liver. Therefore, radiolabelled FIAU is expected to be a useful substrate for non-invasive imaging of HSV1-tk gene therapy and therapeutic response monitoring of HCC.

• Korean Journal of Digital Imaging in Medicine
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• v.14 no.1
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• pp.31-35
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• 2012

To test the real image quality of a spectral attenuated inversion-recovery (SPAIR) fat-suppression (FS) techniquein clinical abdominal MRI by comparison to turbo spin echo inversion-recovery (TSEIR) fat-suppression (FS) technique. 3.0T MRI studies of the abdomen were performed in 30 patients with liver lesions (hemangiomas n: 15; HCC n: 15). T2W sequences were acquired using SPAIR TSEIR. Measurements included retroperitoneal and mesenteric fat signal-to-noise (SNR) to evaluate FS; liver lesion contrast-to-noise (CNR) to evaluate bulk water signal recovery effects; and bowel wall delineation to evaluate susceptibility and physiological motion effects. SPAIR-TSEIR images produce significantly improved FS and liver lesion CNR. The mean SNR of the retroperitoneal and mesenteric fat for SPAIR were 20.5, 10.2 and TSEIR were 43.2, 24.1 (P<0.05). SPAIR-TSEIR images produced higher CNR for both hemangiomas CNR 164.88 vs 126.83 (P<0.05) and metastasis CNR 75.27 vs 53.19 (P<0.05). Bowel wall visualization was significantly improved using in both SPAIR-TSEIR (P< 0.05). The real image quality of SPAIR was better than over conventional TSEIR FS on clinical abdominal MRI scans.