• Journal of Microbiology and Biotechnology
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• v.34 no.4
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• pp.958-968
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• 2024

In recent years, there has been a growing recognition of the important role that long non-coding RNAs (lncRNAs) play in the immunological process of hepatocellular carcinoma (LIHC). An increasing number of studies have shown that certain lncRNAs hold great potential as viable options for diagnosis and treatment in clinical practice. The primary objective of our investigation was to devise an immune lncRNA profile to explore the significance of immune-associated lncRNAs in the accurate diagnosis and prognosis of LIHC. Gene expression profiles of LIHC samples obtained from TCGA database were screened for immune-related genes. The optimal immune-related lncRNA signature was built via correlational analysis, univariate and multivariate Cox analysis. Then, the Kaplan-Meier plot, ROC curve, clinical analysis, gene set enrichment analysis, and principal component analysis were performed to evaluate the capability of the immune lncRNA signature as a prognostic indicator. Six long non-coding RNAs were identified via correlation analysis and Cox regression analysis considering their interactions with immune genes. Subsequently, tumor samples were categorized into two distinct risk groups based on different clinical outcomes. Stratification analysis indicated that the prognostic ability of this signature acted as an independent factor. The Kaplan-Meier method was employed to conduct survival analysis, results showed a significant difference between the two risk groups. The predictive performance of this signature was validated by principal component analysis (PCA). Additionally, data obtained from gene set enrichment analysis (GSEA) revealed several potential biological processes in which these biomarkers may be involved. To summarize, this study demonstrated that this six-lncRNA signature could be identified as a potential factor that can independently predict the prognosis of LIHC patients.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.2
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• pp.184-189
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• 2022

Backgrounds/Aims: The soft texture of the pancreas parenchyma may influence the incidence of pancreatic leakage after pancreaticcoduodenectomy (PD). One possible method to assess pancreatic texture and atrophy, is via computed tomography (CT) scan of the abdomen. The purpose of our study was to evaluate the relation between the preoperative CT scan and the incidence of pancreatic fistula after PD. Methods: A retrospective single-center study including patients who underwent PD for a benign and malignant tumor of the periampullary region between the years 2000 and 2016. Demographic and imaging data were analysed and a correlation with the post-operative leak was evaluated. Results: Pancreatic leak was documented in 34 out of 154 (22.1%) patients. All the leakage cases occurred in the preserved pancreas group (33.1% of the total preserved pancreas group alone). No leak was documented in the atrophic pancreas group. This difference between the two groups was found to be statistically significant (p ≤ 0.00001). Conclusions: Atrophic pancreas in the preoperative CT scan may be protective against leakage after PD. These findings may help the surgeon to risk stratify patients accordingly. In addition, the findings suggest that patients with a preserved pancreas may require more protective methods to prevent leakage.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.243-247
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• 2006

$\underline{Purpose}$: To evaluate the treatment results and prognostic factors of palliative radiation therapy in the patients with unresectable advanced pancreatic cancer. $\underline{Materials\;&\;Methods$: Thirty-seven evaluable patients with unresectable advanced pancreatic cancer who were treated by palliative radiation therapy for pain relief at the Department of Radiation Oncology, Kangnam St. Mary's hospital, the Catholic University of Korea between March 1984 and February 2005 were analysed retrospectively. There were 22 men and 15 women. Age at diagnosis ranged from 30 to 80 (median 57) years. Twelve patients (32.4%) had liver metastases and 22 patients (59.5%) had lymph node metastases. Radiation therapy was delivered to primary tumor and regional lymph nodes with $1{\sim}2\;cm$ margin, and total dose was $3,240{\sim}5,580\;cGy$ (median 5,040 cGy). Chemotherapy with radiotherapy was delivered in 30 patients (81%) with 5-FU alone (21 patients) or gemcitabine (9 patients). The follow-up period ranged from 1 to 44 months. Survival and prognostic factors were analysed using Kaplan-Meier method and log-rank test respectively. $\underline{Results}$: Overall mean and median survival were 11 and 8 months and 1-year survival rate was 20%. Among 33 patients who were amenable for response evaluation, 7 patients had good response and 22 patients had fair response with overall response rate of 87.9%. Mild to moderate toxicity were observed in 14 patients with nausea, vomiting, and indigestion, but severe toxicity requiring interruption of treatment were not observed. Chemotherapy didn't influence the survival and symptomatic palliation, but the group containing gemcitabine showed a tendency of longer survival (median 12 months) than 5-FU alone group (median 5.5 months) without statistical significance (p>0.05). The significant prognostic factors were Karnofsky performance status and liver metastasis (p<0.05). Age, sex, tumor location, lymph node metastasis, and CA 19-9 level did not show any prognostic significance (p>0.05). $\underline{Conclusion}$: Radiation therapy was effective for symptomatic palliation in the patients with unresectable advanced pancreatic cancer and would play an important part in the survival benefit with gemcitabine or other targeted agents.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.123-129
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• 2002

Purpose : The purpose of this study 띤as to determine the potential role of three-dimensional conformal radiotherapy (3D-CRT) in the treatment of primary unresectable hepatocellular carcinoma. The preliminary results on the efficacy and the toxicity of 3D-CRT are reported. Materials and Methods : Seventeen patients were enrolled in this study, which was conducted prospectively from January 1995 to June 1997. The exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child-Pugh classification C, tumors occupying more than two thirds of the entire liver, and a performance status of more than 3 on the ECOG scale. Two patients were treated with radiotherapy only while the remaining 15 were treated with combined transcatheter arterial chemoembolization. Radiotherapy was given to the field including the tumor plus a 1.5 cm margin using a 3D-CRT technique. The radiation dose ranged from $36\~60\;Gy$ (median; 59.4 Gy). Tumor response was based on a radiological examination such as the CT scan, MR imaging, and hepatic artery angiography at $4\~8$ weeks following the completion of treatment. The acute and subacute toxicities were monitored. Results : An objective response was observed in 11 out of 17 patients, giving a response rate of $64.7\%$. The actuarial survival rate at 2 years was $21.2\%$ from the start of radiotherapy (median survival; 19 months). Six patients developed a distant metastasis consisting of a lung metastasis in 5 patients and bone metastasis in one. The complications related to 30-CRT were gastro-duodenitis $(\geq\;grade\;2)$ in 2 patients. There were no treatment related deaths and radiation induced hepatitis. Conclusion : The preliminary results show that 3D-CRT is a reliable and effective treatment modality for primary unresectable hepatocellular carcinoma compared to other conventional modalities. Further studies to evaluate the definitive role of the 3D-CRT technique in the treatment of primary unresectable hepatocellular carcinoma are needed.

• Journal of Life Science
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• v.20 no.5
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• pp.782-788
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• 2010

The protective effects of a powder mixed with solid-cultured and liquid-cultured Lentinus edodes mycelia (2 : 1, w/w) (designate LED) with different doses of carbon tetrachloride ($CCl_4$) on induced hepatotoxicity in male Sprague-Dawley (SD) rats was investigated. The rats were divided into seven groups (6 rats/group) and the following substances were administered orally to each group: Vehicle (0.2 ml distilled water), Control (0.2 ml distilled water), LED (LED 100, 200, 300 and 400 mg/kg BW in 0.2 ml distilled water), and Silymarin (200 mg/Kg BW in 0.2 ml distilled water). After two weeks of daily administration, all groups except for the Vehiclegroup were subjected to abdominal injection with $CCl_4$ ($CCl_4$ : corn oil, 1 : 1 v/v; 0.5 ml/kg BW). One day later, blood and liver samples were collected to analyze biomarkers. All LED treatments elevated hepatic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH peroxidase) activities, and reduced thiobarbituric reactive substances (TBARS), tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and interleukin-6 (IL-6), resulting in the reduction of glutamate-oxalate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactic acid dehydrogenase (LDH) activities in plasma. These results indicate that LED effectively protected SD rat hepatotoxicity induced by $CCl_4$ through its antioxidative activity and reduction of some cytokines. The highest efficacy was found in LED 200 mg/kg BW, showing potential as a useful material for protection from hepatotoxicity in humans.

• Radiation Oncology Journal
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• v.29 no.1
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• pp.36-43
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• 2011

Purpose: To evaluate the effectiveness of radiation therapy (RT) for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and to analyze the prognostic factors. Materials and Methods: From December 2004 to April 2009, 70 patients who had HCC with PVTT were treated with RT at Keimyung University Dongsan Medical Center. Nineteen patients whose total dose was below 30 Gy and one patient who underwent liver transplantation were excluded. The remaining 50 patients (45 males, 5 females; median age 55 years) were analyzed. According to the LCSGJ TNM stage, there were 27 patients (54.0%) with stage III and 23 (46.0%) with stage IV. Total dose of 30~54 Gy was administered (median 45). Thirty patients (60.0%) were treated with concurrent chemoradiation therapy (CCRT). The median follow-up duration was from 13.5 months (range, 3 to 70 months). Results: The median survival time from the start of RT was 9 months. One-year and 2-year overall survival rates were 24.9% and 11.2%, respectively. At the follow-up time, three patients (6.0%) displayed no evidence of disease. Seven patients (14.0%) were alive with disease, and 40 (80.0%) patients had expired due to disease progression. CCRT was associated with worse survival than RT alone (p=0.034), Response to RT (p=0.037), CLIP stage (p=0.017), and TNM stage (p=0.041) were statistically significant prognostic factors. There was no radiation-induced liver disease. Conclusion: RT is an effective and safe modality for HCC with PVTT. Further studies such as prospective randomized trials are needed to confirm the role of RT for HCC with PVTT.

• Journal of Life Science
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• v.31 no.11
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• pp.1028-1036
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• 2021

Firefly luciferase (FLuc) can function as an efficient marker in the gene and viral therapies. Nonetheless, its clinical translation has been unaccomplished with the concerns on its exogenous nature and the similarity with human fatty acyl-CoA synthetase. In this study, we aimed to show safety of FLuc by conducting a set of preclinical experiments and a human use. Initially, FLuc permeability across the plasma membrane was investigated by delivering the FLuc-carrying viral vector, OTS-412, or the FLuc recombinant protein. After in vitro infection of OTS-412 into different cancer cell lines, FLuc activity was detected only in the cell lysates, but not in culture media. In addition, recombinant FLuc protein further showed the impermeability against the plasma membrane. Similar result was also observed in the in vivo experiment. After being injected into the VX2 tumor-bearing rabbit, the FLuc exclusively resided within the tumor tissue without being detected in the blood plasma or other organs. Human cancer cell lines originated from various organs were lysed and treated to the FLuc, and none of the human substrates was reactive against the FLuc. As a final step, FLuc recombinant protein was intravenously injected into a human. The luciferase was degraded with the half-life of 20 to 30 minutes in blood, and was untraceable from 1.5 hr after the injection. In addition, the blood plasma was nonresponsive against the fatty acids. Hematological analysis was also comparable between the pre- and post-injection. Altogether, our study collectively demonstrates the safety of the firefly luciferase.

• Progress in Medical Physics
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• v.25 no.2
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• pp.79-88
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• 2014

The dose distributions within the real volumes of tumor targets and critical organs during internal target volume-based intensity-modulated radiation therapy (ITV-IMRT) for liver cancer were recalculated by applying the effects of actual respiratory organ motion, and the dosimetric features were analyzed through comparison with gating IMRT (Gate-IMRT) plan results. The ITV was created using MIM software, and a moving phantom was used to simulate respiratory motion. The doses were recalculated with a 3 dose-volume histogram (3DVH) program based on the per-field data measured with a MapCHECK2 2-dimensional diode detector array. Although a sufficient prescription dose covered the PTV during ITV-IMRT delivery, the dose homogeneity in the PTV was inferior to that with the Gate-IMRT plan. We confirmed that there were higher doses to the organs-at-risk (OARs) with ITV-IMRT, as expected when using an enlarged field, but the increased dose to the spinal cord was not significant and the increased doses to the liver and kidney could be considered as minor when the reinforced constraints were applied during IMRT plan optimization. Because the Gate-IMRT method also has disadvantages such as unsuspected dosimetric variations when applying the gating system and an increased treatment time, it is better to perform a prior analysis of the patient's respiratory condition and the importance and fulfillment of the IMRT plan dose constraints in order to select an optimal IMRT method with which to correct the respiratory organ motional effect.

• Journal of Radiation Protection and Research
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• v.39 no.4
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• pp.168-175
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• 2014

This study was designed to assess whether the conventional tangential technique, using a multileaf collimator (MLC), allows a reduced dose to the organs at risk (OAR) in breast radiation therapy. A total of forty right and left 20 for each breast cancer patients that underwent radiation therapy after breast conserving surgery were included in this study. For each patient, the planning target volume (PTV) and OAR (heart, left anterior descending artery (LAD), liver and lung) were defined and dose distribution were produced for conventional tangential beams using 6 MV photons. The treatment plans were made using the following two techniques for all patients. For the first plan (P1), MLC was designed to shield as much of OAR as possible without compromising the coverage of PTV. In the second plan (P2), the treatment plan was created without using MLC. Dose-volume histograms for OARs were calculated for all plans. For left breast cancer, the percentage of maximum dose ($D_{max%}$) and mean dose ($D_{mean%}$) of OARs (heart and LAD) were calculated, and for right breast cancer, the percentage of the mean dose ($D_{mean%}$) of the liver was calculated. The $D_{mean%}$ of the lung was calculated in all patients. The mean values of $D_{max%}$ of the heart ($86.9{\pm}19.5%$ range, 35.1-100.6%) in P1 were significantly lower than in P2 ($98.3{\pm}3.4%$ range, 91.7-105.2%) (p=0.001). The mean values of $D_{max%}$ of LAD ($78.4{\pm}22.5%$ range, 26.5-99.7%) in P1 was significantly lower than in P2 ($93.3{\pm}8.1%$ range, 67.9-102.1%) (p<0.001). In P1, the mean values of $D_{mean%}$ of the liver ($4.8{\pm}2.0%$) were significantly lower than in P2 ($6.2{\pm}2.5%$) (p<0.001). The mean values of $D_{mean%}$ of the lung were significantly lower in P1 ($9.3{\pm}2.3%$) than in P2 ($9.7{\pm}2.4%$) (p<0.001). P1, by using MLC, allows a significantly reduced dose to OAR compared with P2. We can suggest that it is reasonable to routinely use MLC in the conventional tangential technique for breast radiation therapy considering the primary tumor location.

• Journal of Life Science
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• v.24 no.6
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• pp.664-670
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• 2014

In the present study, we investigate the role of V. vulnificus in promoting the inflammation of mouse ileal ephitelium and its related signaling pathways. ICR mice were infected orally with V. vulnificus ($1{\times}10^9CFU$) for 16 h as a representative model of food-borne infection. To find the major portal of entry of V. vulnificus in mouse intestine, we have measured the levels of bacterial colonization in small intestine, colon, spleen, and liver. V. vulnificus appeared to colonize in intestine and colon in the order of ileum >> jejunum> colon, but lack in the duodenum, spleen, and liver. V. vulnificus in ileum caused severe necrotizing enteritis and showed shortened villi heights accompanied by an expanded width and inflammation, compared with the control mice. V. vulnificus induced ileal epithelium inflammation by activating phosphorylation of PKC and membrane translocation of $PKC{\alpha}$. V. vulnificus induced the phosphorylation of ERK and JNK, but did not affect p38 MAPK phosphorylation. Notably, V. vulnificus stimulated the I-${\kappa}B$-dependent phosphorylation of NF-${\kappa}B$ in mouse ileal epithelium. Finally, the ileal infection of V. vulnificus resulted in a significant increase in expression of proinflammatory cytokines and Toll-like receptors, respectively, compared to the control. Collectively, our results indicate that V. vulnificus induces ileal epithelium inflammation by increasing NF-${\kappa}B$ phosphorylation via activation of PKC, ERK, and JNK, which is critical for host defense mechanism in food-borne infection by V. vulnificus.