• 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.

• Journal of Life Science
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• v.33 no.1
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• pp.15-24
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• 2023

To examine the antitumor effect of proso millet grains, whether proso millet grains exert apoptotic activity against human cancer cells was investigated. When the cytotoxicity of 80% ethanol (EtOH) extract of proso millet grains was tested against various cancer cells using MTT assay, more potent cytotoxicity was observed against human breast cancer MDA-MB-231 cells than against other cancer cells. When the EtOH extract was evaporated to dryness, dissolved in water, and then further fractionated by sequential extraction using four organic solvents (n-hexane, methylene chloride, ethyl acetate, and n-butanol), the BuOH fraction exhibited the highest cytotoxicity against MDA-MB-231 cells. Along with the cytotoxicity, TUNEL-positive apoptotic nucleosomal DNA fragmentation and several apoptotic responses including BAK/BAX activation, mitochondria membrane potential (Δψm) loss, mitochondrial cytochrome c release into the cytosol, activation of caspase-8/-9/-3, and degradation of poly (ADP-ribose) polymerase (PARP) were detected. However, human normal mammary epithelial MCF-10A cells exhibited a significantly lesser extent of sensitivity compared to malignant MDA-MB-231 cells. Irrespective of Fas-associated death domain (FADD)-deficiency or caspase-8-deficiency, human T acute lymphoblastic leukemia Jurkat cells displayed similar sensitivities to the cytotoxicity of BuOH fraction, excluding an involvement of extrinsic apoptotic mechanism in the apoptosis induction. These results demonstrate that the cytotoxicity of BuOH fraction from proso millet grains against human breast cancer MDA-MB-231 cells is attributable to intrinsic apoptotic cell death resulting from BAK/BAX activation, and subsequent mediation of mitochondrial damage-dependent activation of caspase cascade.

• Journal of Marine Life Science
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• v.8 no.2
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• pp.136-149
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• 2023

Basic bioactivities (antioxidant, anti-inflammatory, antibacterial, anticancer, antiviral) were investigated from 370 strains of marine bacteria, fungi, and microalgae obtained from various marine environmental regions in Korea, and the activity results were obtained at the collection site, isolation source, and species level was compared. In the case of marine bacteria, strains belonging to the generally useful genera Streptomyces and Bacillus were observed to have particularly strong efficacy and useful resources were mainly isolated from marine sediments. In the case of marine fungi and microalgae, results showing strong species-specific activity were confirmed, and results showing efficacy-specific activity were also obtained. Based on these results, it is a research result that can facilitate priority access as a strategic material for industrial revitalization and the establishment of a strategy to secure resources based on usefulness when conducting research on chemicals that are selectively effective against specific diseases or when conducting resource-based research. In addition, we believe that by using these results as material for sale through the Marine BioBank (MBB), academia and industry can use them to help accelerate the revitalization of the marine bio industry.

• Journal of Life Science
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• v.34 no.5
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• pp.313-319
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• 2024

Cultivars or genetic resources with a black seed coat and green cotyledons are rich in lutein, which can promote eye health, and anthocyanin, known for its numerous health benefits. However, mature seeds also contain P34, 7S α' subunit, and lectin proteins, which are allergenic and degrade quality. Here, we report the breeding of a new soybean line with a black seed coat, green cotyledon, and free of P34, 7S α' subunit, and lectin proteins. A total of 157 F₂ seeds with black seed coats and green cotyledons were selected by crossing a female parent with a brown seed coat, green cotyledon, and lacking the 7S α' subunit and lectin proteins with a male parent with a black seed coat, green cotyledon, and lacking the P34 and lectin proteins. The P34 and 7S α' subunit proteins were consistent with a ratio of 9:3:3:1, indicating that they are independent of each other. From 14 F₂ seeds that were recessive (cgy1cgy1p34p34) for both proteins, one individual F₂ plant (F₃ seeds) with the desired traits-black seed coat, green cotyledon, and lacking P34, 7S α' subunit, and lectin proteins- was finally selected. The triple null genotype (absence for P34, 7S α' subunit, and lectin proteins) was confirmed in random F₃ seeds. The selected line has a black seed coat and green cotyledons, and when sown on June 14 in the greenhouse, the maturity date was approximately October 3, the height was about 68 cm, and the 100-seed weight was about 26.5 g.

• Journal of the Korean Society of Radiology
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• v.84 no.5
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• pp.1094-1109
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• 2023

Purpose To investigate whether CT-based tumor regression grade (ctTRG) can be used to predict the response to neoadjuvant chemotherapy (NAC) in colon cancer. Materials and Methods A total of 53 patients were enrolled. Two radiologists independently assessed the ctTRG using the length, thickness, layer pattern, and luminal and extraluminal appearance of the tumor. Changes in tumor volume were also analyzed using the 3D Slicer software. We evaluated the association between pathologic TRG (pTRG) and ctTRG. Patients with Rödel's TRG of 2, 3, or 4 were classified as responders. In terms of predicting responder and pathologic complete remission (pCR), receiver operating characteristic was compared between ctTRG and tumor volume change. Results There was a moderate correlation between ctTRG and pTRG (ρ = -0.540, p < 0.001), and the interobserver agreement was substantial (weighted κ = 0.672). In the prediction of responder, there was no significant difference between ctTRG and volumetry (Az = 0.749, criterion: ctTRG ≤ 3 for ctTRG, Az = 0.794, criterion: ≤ -27.1% for volume, p = 0.53). Moreover, there was no significant difference between the two methods in predicting pCR (p = 0.447). Conclusion ctTRG might predict the response to NAC in colon cancer. The diagnostic performance of ctTRG was comparable to that of CT volumetry.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.127-135
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• 2001

Purpose : This study is a prospective randomized clinical trial comparing the efficacy and complication of anti-emetic drugs for prevention of nausea and vomiting after radiotherapy which has moderate emetogenic potential. The aim of this study was to investigate whether the anti-emetic efficacy of ondansetron $(Zofran^{\circledR})$ 8 mg bid dose (Group O) is better than the efficacy of metoclopramide 5 mg lid dose (Group M) in patients undergoing fractionated radiotherapy to the abdominal region. Materials and Methods : Study entry was restricted to those patients who met the following eligibility criteria: histologically confirmed malignant disease; no distant metastasis; performance status of not more than ECOG grade 2; no previous chemotherapy and radiotherapy. Between March 1997 and February 1998, 60 patients enrolled in this study. All patients signed a written statement of informed consent prior to enrollment. Blinding was maintained by dosing identical number of tablets including one dose of matching placebo for Group O. The extent of nausea, appetite loss, and the number of emetic episodes were recorded everyday using diary card. The mean score of nausea, appetite loss and the mean number of emetic episodes were obtained in a weekly interval. Results : Prescription error occurred in one patient. And diary cards have not returned in 3 patients due to premature refusal of treatment. Card from one patient was excluded from the analysis because she had a history of treatment for neurosis. As a result, the analysis consisted of 55 patients. Patient characteristics and radiotherapy characteristics were similar except mean age was $52.9{\pm}11.2$ in group M, $46.5{\pm}9.5$ in group O. The difference of age was statistically significant. The mean score of nausea, appetite loss and emetic episodes in a weekly interval was higher in group M than O. In group M, the symptoms were most significant at 5th week. In a panel data analysis using mixed procedure, treatment group was only significant factor detecting the difference of weekly score for all three symptoms. Ondansetron $(Zofran^{\circledR})$ 8 mg bid dose and metoclopramide 5 mg lid dose were well tolerated without significant side effects. There were no clinically important changes In vital signs or clinical laboratory parameters with either drug. Conclusion : Concerning the fact that patients with younger age have higher emetogenic potential, there are possibilities that age difference between two treatment groups lowered the statistical power of analysis. There were significant difference favoring ondansetron group with respect to the severity of nausea, vomiting and loss of appetite. We concluded that ondansetron is more effective anti-emetic agents in the control of radiotherapy-induced nausea, vomiting, loss of appetite without significant toxicity, compared with commonly used drug, i.e., metoclopramide. However, there were patients suffering emesis despite the administration of ondansetron. The possible strategies to improve the prevention and the treatment of radiotherapy-induced emesis must be further studied.

• The Korean Journal of Nuclear Medicine Technology
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• v.16 no.1
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• pp.57-61
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• 2012

Purpose: The multi-gated cardiac blood pool scan is to evaluate the function of left ventricle (LV) and usefully observe a value of ejection fraction (EF) for a patient who is receiving chemotherapy. To calculate LVEF, we should adjust an angle of left anterior oblique (LAO) view to separate both ventricles. And by overlapped ventricles, it is possible to affect LVEF. The purpose of this study is to investigate and compare quantitative indices by changing an angle of LAO view. Materials and methods: We analyzed the 49 patients who were examined by multi-gated cardiac blood pool scan in department of nuclear medicine at Asan Medical Center from June to September 2011. Firstly, we acquired "Best septal" view. And then, we got images by addition and subtraction of angle for LAO view to anterior and lateral. We compared three LAO views for 20 people by 5 degrees and 39 people by 10 degrees. And we analyzed quantitative indices, EF, end diastole and end systole counts, by automated and manual region of interest (ROI) modes. Results: Firstly, we analyzed quantitative indices by automated ROI mode. In case of 5 degrees, the averages of EF are $61.0{\pm}7.5$, $62.1{\pm}7.1$, $60.9{\pm}6.7%$ ($p$=0.841) in LAO, LAO $-5^{\circ}$ and LAO $+5^{\circ}$ respectively. And there is no difference in end diastole and end systole counts ($p$<0.05). In case of 10 degrees, the averages of EF are $62.4{\pm}9.5$, $62.3{\pm}10.8$, $61.6{\pm}.9.3%$ ($p$=0.938) in LAO, LAO $-10^{\circ}$ and LAO $+10^{\circ}$ respectively. And there is no difference in end diastole and end systole counts ($p$<0.05). Secondly, we analyzed quantitative indices by manual ROI mode. In case of 5 degrees, the averages of EF are $62.8{\pm}7.1$, $63.6{\pm}7.5$, $62.7{\pm}7.3%$ ($p$=0.903) in LAO, LAO $-5^{\circ}$ and LAO $+5^{\circ}$ respectively. And there is no difference in end diastole and end systole counts ($p$<0.05). In case of 10 degrees, the averages of EF are $65.5{\pm}9.0$, $66.3{\pm}8.7$, $63.5{\pm}.9.3%$ (p=0.473) in LAO, LAO $-10^{\circ}$ and LAO $+10^{\circ}$ respectively. And there is no difference in end diastole and end systole counts ($p$<0.05). Conclusion: When an image is nearly "Best septal" view, the difference of LAO angle would not affect to change LVEF. Although there was no difference in quantitative analysis, deviations could happen when to interpret wall motion qualitatively by reading physicians.

• The Korean Journal of Nuclear Medicine Technology
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• v.20 no.2
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• pp.3-8
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• 2016

Purpose SUV is one of the parameters that assist diagnosis in origin, metastasis and staging of cancer. Specially, it is important to compare SUV before and after chemo or radiation therapy to find out effectiveness of treatment. Storing PET data which has no quantitative change is needed for SUV comparison. However, there is a possibility to loss the data in external hard drive or MINIpacs that are managed by department of nuclear medicine. The aim of this study is to evaluate SUV and metabolic tumor volume (MTV) among reconstructed data (R-D) in workstation, R-D and re-sliced data (S-D) in PACS. Materials and Methods Data of 20 patients (aged $60.5{\pm}8.3y$) underwent $^{18}F-FDG$ PET (Biograph truepoint 40, mCT 40, mCT 64, mMR, Siemens) study were analysed. $SUV_{max}$, $SUV_{peak}$ and MTV were measured in liver, aorta and tumor after sending R-D in workstation, R-D and S-D in PACS to syngo.via software. Results R-D of workstation and PACS showed the same value as mean $SUV_{max}$ in liver, aorta and tumor were $2.95{\pm}0.59$, $2.35{\pm}0.61$, $10.36{\pm}6.15$ and $SUV_{peak}$ were $2.70{\pm}0.51$, $2.07{\pm}0.43$, $7.67{\pm}3.73$(p>0.05) respectively. Mean $SUV_{max}$ of S-D in PACS were decreased by 5.18%, 7.22%, 12.11% and $SUV_{peak}$ 2.61%, 3.63%, 10.07%(p<0.05). Correlation between R-D and S-D were $SUV_{max}$ 0.99, 0.96, 0.99 and $SUV_{peak}$ 0.99, 0.99, 0.99. And 2SD in balnd-altman analysis were $SUV_{max}$ 0.125, 0.290, 1.864 and $SUV_{peak}$ 0.053, 0.103, 0.826. MTV of R-D in workstation and PACS show the same value as $14.21{\pm}12.72cm^3$(p>0.05). MTV in PACS was decreased by 0.12% compared to R-D(p>0.05). Correlation and 2SD between R-D and S-D were 0.99 and 2.243. Conclusion $SUV_{max}$, $SUV_{peak}$, MTV showed the same value in both of R-D in workstation and PACS. However, there was statistically difference in $SUV_{max}$, $SUV_{peak}$ of S-D compare to R-D despite of high correlation. It is possible to analyse reliable pre and post SUV if storing R-D in main hospital PACS system.

• Radiation Oncology Journal
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• v.10 no.2
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• pp.247-253
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• 1992

Between August 1987 and July 1991, 22 patients with acute nonlymphocytic leukemia have received allogeneic bone marrow transplantation (BMT) with non-T-lymphocyte-depleted marrow obtained from matched sibling donors. Of these patients, 12 patients were in first complete remission (CR) and 10 patients in second CR or greater or in relapse. All patients were treated with a preparative regimen consisting of cyclophosphamide (CTX, 60 mg/kg) or combined drugs, and 850 cGy single-dose or $150\~200$ cGy fractionated total body irradiation (TBI) administered twice daily for a total dose of $1200\~1320$ cGy. Survivors have been followed from 8 to 64.5 months (median, 24 months). The overall 2 year survival rate, relapse rate and incidence of radiation pneumonitis and graft versus host disease (GVHD) have been evaluated by age, phase of disease, initial WBC count, modality of TBI or conditioning chemotherapy. Overall 2 year survival was $58{\%}$. The median survival was 31 months and mean survival was 23.2 months. Overall survival have significant impact in patients of age >19 years old (p=0.008), patients in first CR (p=0.09). Two year survival rate is significantly correlated with age ( >19 vs $\leqq$19, $79.4\%$ vs $14.3\%$, p=0.0008), regimen of chemotherapy (CTX vs combined drug, $76.9\%\;vs\;33.3\%$, p=0.04), phase of disease (1st CR vs \geqq2nd$ CR or relapse, $83.3\%\;vs\;30\%$, p=0.01) and method of TBI (fractionated vs single dose, $70.7\%\;vs\;37.5\%$, p=0.05). The influence of French-American-British (FAB) subtypes on relapse rate is not significant, but initial WBC count > 20000/$mm^3$ is associated with increased relapse rate. There is difference in the rate of radiation pneumonitis ($14.3\%\;vs\;25\%$), GVHD ($14.3\%\;vs\;50\%$) and relapse ($21.4\%\;vs\;50\%$) according to fractionated versus single-dose TBI. As mentioned above, fractionated TBI is compatible for the preparative regimen combined with chemotherapy En allogeneic BMT of first CR patients under 41 years of age with suitable donor. Those results from a retrospective, non-randomized study clearly need additional clinical data, ideally from a randomized study.

• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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• pp.168-184
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• 2001

Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.