• Journal of Gastric Cancer
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• v.23 no.3
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• pp.476-486
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• 2023

Purpose: The optimal tumor mutational burden (TMB) value for predicting treatment response to programmed cell death-1 (PD-1) checkpoint inhibitors in advanced gastric cancer (AGC) remains unclear. We aimed to investigate the optimal TMB cutoff value that could predict the efficacy of PD-1 checkpoint inhibitors in AGC. Materials and Methods: Patients with AGC who received pembrolizumab or nivolumab between October 1, 2020, and July 27, 2021, at Samsung Medical Center in Korea were retrospectively analyzed. The TMB levels were measured using a next-generation sequencing assay. Based on receiver operating characteristic curve analysis, the TMB cutoff value was determined. Results: A total 53 patients were analyzed. The TMB cutoff value for predicting the overall response rate (ORR) to PD-1 checkpoint inhibitors was defined as 13.31 mutations per megabase (mt/Mb) with 56% sensitivity and 95% specificity. Based on this definition, 7 (13.2%) patients were TMB-high (TMB-H). The ORR differed between the TMB-low (TMB-L) and TMB-H (8.7% vs. 71.4%, P=0.001). The progression-free survival and overall survival (OS) for 53 patients were 1.93 (95% confidence interval [CI], 1.600-2.268) and 4.26 months (95% CI, 2.992-5.532). The median OS was longer in the TMB-H (20.8 months; 95% CI, 2.292-39.281) than in the TMB-L (3.31 months; 95% CI, 1.604-5.019; P=0.049). Conclusions: The TMB cutoff value for predicting treatment response in AGC patients who received PD-1 checkpoint inhibitor monotherapy as salvage treatment was 13.31 mt/Mb. When applying the programmed death ligand-1 status to TMB-H, patients who would benefit from PD-1 checkpoint inhibitors can be selected.

• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.302-313
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• 1995

Background: Tumor necrosis factor(TNF) showed antitumor cytolytic effects on sensitive tumor cells in numerous in vivo and in vitro studies. But it could not be administered systemically to human because of severe systemic adverse effects at effective concentrations against tumor cells. Many studies showed that a high concentrations of TNF in the local milieu may evoke in vivo TNF-responsive mechanisms sufficient to suppress tumor growth. Recently developed technique of TNF gene transfer to tumor cells using retrovirus vector could be a good candidate for local TNF administration. TNF is also known to synergistically enhance in vitro cytotoxicity of chemotherapeutic drugs targeted to DNA topoisomerase II against TNF-sensitive tumor cell lines. In this study the in vitro chemosensitivity against DNA topoisomerase II targeted chemotherapeutic drugs was evaluated using some respiratory cancer cell lines to which TNF gene had been transferred. Method: NCI-H2058, a human mesothelioma cell line, A549, a human lung adenocarcinoma cell line and WEHI 164 cell line, a murine fibrosarcoma cell line were treated with etoposide and doxorubicin, which are typical topoisomerase II - targeted chemotherapeutic agents, at different concentration. The resultant cytotoxicity was measured by MIT assay. Then the cytotoxicity of the same chemotherapeutic agents was measured after TNF-$\alpha$ gene-transfer and the two results were compared. Results: The cytotoxicity was not increased significantly in WEHI164 cell line and A549 cell line but statistically significant increase was observed in H2058 cell line when TNF-$\alpha$ gene was transferred(p<0.05). Conclusion: These findings show that TNF-$\alpha$ gene transfer to respiratory cancer cell lines results in variable effects on chemosensitivity against topoisomerase II inhibitor among different cell lines in vitro and can be additively cytotoxic in certain selective tumor cell lines.

• Parasites, Hosts and Diseases
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• v.30 no.4
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• pp.299-307
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• 1992

An antigenic protein in cystic quid of Taenia solium metacestodes (CF) of 150 kDa was measured by antibody-sandwich ELISA in serum and cerebrospinal quid (CSF) of neurocysticercosis patients. Capture antibodies were rabbit antisera against CF (RACF) and a monoclonal antibody (MAb) against 150 kDa protein in CF. Lower limit of antibody-sandwich ELISA was 8 ng/ml of the protein. Except CF, no tested helminthes extracts reacted. Levels of the protein in 351 sera from 255 patients (55 surgery confirmed and 202 antibody and CT/MRl confirmed) were below sensitivity of the assay. Of 276 CSF from 212 patients, 31 samples (11.2%) showed positive findings. This assay, therefore, was not sensitive enough to be a diagnostic. Instead, the 150 kDa protein appeared in CSF in such situations as in 2 days after prasiquantel treatment, or as in a patient infected with a racemose cysticercus with degenerated cyst wall. Of cases whose follow-up CSF were assayed, 2 cases showed that the protein appeared intermittently, These results suggest strongly that appearance of free 150 kDa protein is associated with cyst wall rupture. In CSF which contained the 150 kDa protein over 61 ng/ml, the protein was recognized in 505-PAGE before and after immunoprecipitation.

• Clinical and Experimental Pediatrics
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• v.49 no.1
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• pp.87-92
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• 2006

Purpose : It is difficult to make a distinction between lower urinary tract infection(UTI) and acute pyelonephritis(APN) during the acute phase of febrile UTI due to nonspecific clinical symptoms and laboratory findings, especially among young children. We measured the serum procalcitonin(PCT) in children with UTI to distinguish between acute pyelonephritis and lower UTI, and to determine the accuracy of PCT measurement compared with other inflammatory markers. Methods : Serum samples were taken from children who admitted with unexplained fever or were suspected of having UTI. 51 children(mean $12.2{\pm}11.4$ months) were enrolled in this study. Leukocyte counts, erythrocyte sedimentation rates(ESR) and C-reactive protein(CRP) were also measured. Renal parenchymal involvement was assessed by $^{99m}Tc$ DMSA scintigraphy in the first 7 days after admission. PCT was measured by immunoluminometric assay. Results : PCT values were significantly correlated with the presence of renal defects in children with UTI(n=16)($5.06{\pm}12.97{\mu}g/L$, P<0.05). However, PCT values were not significantly different between children with UTI without renal damage(n=18) and children without UTI(n=17). Using a cutoff of $0.5{\mu}g/L$ for PCT and 20 mm/hr for ESR, 20 mg/L for CRP, sensitivity and specificity in distinguishing between UTI with and without renal involvement were 81.3 percent and 88.9 percent for PCT 87.5 percent and 72.2 percent for ESR, and 87.5 percent and 55.6 percent for CRP, respectively. Positive and negative predictive values were 86.7 percent and 84.2 percent for PCT and 60.9 percent and 81.8 percent for CRP, respectively. Conclusion : In febrile UTI, PCT values were more specific than CRP, ESR and leukocyte count for the identification of patients who might develop renal defects.

• Asian Journal of Turfgrass Science
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• v.20 no.1
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• pp.65-76
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• 2006

Scz1, an isolate of Sclerotinia homoeocarpa, was recently reported as a novel pathogen responsible for dollar spot disease in Zoysiagrass, a warm season turfgrass. Scz1 possessed different characteristics on mycelial pigment, mycelial affinity and host pathogenecity compared to those of Scb1, a typical isolate, obtained from creeping bentgrass, a cool season turfgrass. In this study, only three isolates, Scz1, Scz2(another analogous isolate of Sclerotinia homoeocarpa from zoysiagrass), and Scb1, were examined at the molecular level using the internal transcribed spacer(ITS) and random amplified polymorphic DNA(RAPD) assays to verify their identification and genetic variation. As a result of ITS assay, partial ITS sequences of three isolates showed 94-97% similarity with a standardized ITS sequence of S. homoeocarpa registered on BLAST. In the analysis of RAPD, range value through similarity matrix was 0.167 between Scz1 and Scb1, 0.139 between Scz2 and Scb1, and 0.713 between Scz1 and Scz2, respectively. Furthermore, tendegram analysis indicated that Scz1 and Scz2, unlike Scb1, were clustered together as accompanying a high genetic similarity. In in vitro fungicide bioassay, $EC_{50}$ value representing the sensitivity degree to propiconazole, a well-known fungicide for dollar spot disease, was 0.012 ${\mu}g/ml$ for Sczl, 0.003 ${\mu}g/ml$ for Scz2, and 0.030 ${\mu}g/ml$ for Scb1. From all data taken, we concluded that both Scz1 and Scz2 belonged to one group of S. homoeocarpa, since they exhibit the same host range and high level of genetic similarity, whereas their chemical competences to a fungicide were different. This study would provide further approach for assessing genetic diversity of S. homoeocarpa isolates as well as characterizing individual isolate against chemical exposure.

• Pediatric Infection and Vaccine
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• v.15 no.1
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• pp.52-58
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• 2008

Purpose : Whole blood interferon-$\gamma$ assay was developed and many studies showed its usefulness in diagnosing tuberculosis (TB) including latent tuberculosis infection (LTBI). However, assessment in children has been limited. This study was undertaken to evaluate the usefulness of QuantiFERON-TB Gold for the diagnosis of LTBI in children exposed to pulmonary TB. Methods : Children who visited Seoul National University Bundang Hospital with a history of TB exposure were enrolled from January 2006 to December 2007. They were evaluated with chest x-rays, tuberculin skin test (TST) and QuantiFERON-TB Gold test. TST was retested 3 months later for those with initial negative reactivity. Definition of LTBI was made on the basis of the TST reactivity. Results : Among the 103 children with a history of TB exposure, 49 children were tested with chest x-ray, TST, and QuantiFERON-TB Gold. Twenty-two were males. Median age was 7.5 years (range; 3 months to 14.7 years). According to TST reactivity, LTBI was in 8 (19%), no infection was in 21 (50%), possible LTBI was in 13 (31%). QuantiFERON-TB Gold test was positive in 5 of the 49 subjects (10%); 3 of the 13 subjects (23.1%) in unknown status, 1 of the 8 subjects (13%) in LTBI, and 1 of the 21 subjects (5%) without infection. The agreement between the QuantiFERON-TB Gold and the TST was poor (${\kappa}=0.101$). Conclusion : QuantiFERON-TB Gold showed poor sensitivity for the diagnosis of LTBI in children with exposure to TB. QuantiFERON-TB Gold alone does not seem to be useful in the diagnosis of LTBI in children.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.197-206
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• 1997

Purpose : Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid (PA) and choline. Recently, PLD has been drawing much attentions and considered to be associated with cancer Process since it is involved in cellular signal transduction. In this experiment, oleate-PLD activities were measured in various tissues of the living rats after whole body irradiation. Materials and Methods : The reaction mixture for the PLD assay contained $0.1\;\muCi\;1,2-di[1-^{14}C]palmitoyl$ phosphatidylcholine 0.5mM phosphatidylcholine, 5mM sodium oleate, $0.2\%$ taurodeoxycholate, 50mM HEPES buffer(pH 6.5), 10mM $CaCl_2$, and 25mM KF. phosphatidic acid, the reaction product, was separated by TLC and its radioactivity was measured with a scintillation counter. The whole body irradiation was given to the female Wistar rats via Cobalt 60 Teletherapy with field size of 10cmx loom and an exposure of 2.7Gy per minute to the total doses of 10Gy and 25Gy. Results : Among the tissues examined, PLD activity in lung was the highest one and was followed by kidney, skeletal muscle, brain, spleen, bone marrow, thymus, and liver. Upon irradiation, alteration of PLD activity was observed in thymus, spleen, lung, and bone marrow. Especially PLD activities of the spleen and thymus revealed the highest sensitivity toward $\gamma-rar$ with more than two times amplification in their activities In contrast, the PLD activity of bone marrow appears to be reduced to nearly $30\%$. Irradiation effect was hardly detected in liver which showed the lowest PLD activity. Conclusion : The PLD activities affected most sensitively by the whole-body irradiation seem to be associated with organs involved in immunity and hematopoiesis. This observation s1ron91y indicates that the PLD is closely related to the physiological function of these organs, Furthermore, radiation stress could offer an important means to explore the phenomena covering from cell Proliferation to cell death on these organs.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.145-154
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• 2004

Purpose : To examine whether a synthetic bile acid derivatives (HS-1200) sensitizes the radiation-induced apoptosis in human breast cancer cells (MCF-7) and to investigate the underlying mechanism. Materials and Methods : Human breast cancer cells (MCF-7) in exponential growth phase were treated with HS-1200 for 24 hours at 37$^{\circ}C$ with 5$\%$ CO$_{2}$ in air atmosphere. After removal of HS-1200, cells were irradiated with 2$\~$8 Gy X-ray, and then cultured Ii drug-free media for 24-96 hours. The effect of radiation on the clonogenicity of MCF-7 cells was determined with clonogenic cell survival assay with 16$\mu$M of HS-1200. The induction of apoptosis was determined using agarose gel electrophoresis and Hoechst staining. The expression level of apoptosis-related molecules, such as PARP, Bax, Bcl-2, Bak and AIF, were assayed by Western blotting analysis with 40$\mu$M of HS-1200 combined with 8 Gy irradiation. To examine the cellular location of cytochrome c, bax and AIF immunofluorescent stainings were undertaken. Results : Treatment of MCF-7 cells with 40$\mu$M of HS-1200 combined with 8 Gy irradiation showed several changes associated with enhanced apoptosis by agarose gel electrophoresis and Hoechst staining. HS-1200 combined with 8 Gy irradiation treatment also enhanced production of PARP cleavage products and increased Bax/Bcl-2 ratio by Western blotting. Loss of mitochondrial membrane potential ($\Delta$$\psi$$_{m}$) and increased cytochrome c staining indicated that cytochrome c had been released from the mitochondria in HS-1200 treated cells. Conclusion : We demonstrated that combination treatment with a synthetic chenodeoxycholic acid derivative HS-1200 and irradiation enhanced radiation-induced apoptosis of human breast cancer cells (MCF-7). We suggest that the increased Bax/Bcl-2 ratio In HS-1200 co-treatment group underlies the increased radio sensitivity of MCF-7 cells. Further futures studies are remained elusive.

• Tuberculosis and Respiratory Diseases
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• v.55 no.4
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• pp.388-394
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• 2003

Background : Monoclonal antibodies directed against well-known epitopes on cytokeratin (CK) 8, 18 and 19 (Monototal) have been used in the development of a new diagnostic tool for lung cancer. In the mid-1990s, CK 19 fragments (Cyfra 21-1) became popular and widely used for such diagnosis. This is the first study specifically designed to compare these two markers. Method : The serum levels of CK 8, 18 and 19 were measured using two-site monoclonal/polyclonal immunoradiometric assay kit in 57 healthy adults and 289 patients who were admitted to Seoul National University Hospital from May to September, 2002. The lung cancer group comprised 129 primary lung cancer patients; 116 with non-small cell lung cancer(NSCLC) and 13 with small cell lung cancer (SCLC). The control group comprised 160 non-malignant pulmonary lung disease patients and 57 healthy adults. A total of 166 twin Monototal and Cyfra 21-1 serum assays were obtained; 76 with lung cancer, 70 with non-malignant pulmonary lung disease and 20 healthy adults. Results : The mean serum value of Monototal was $412.47{\pm}455.45U/L$ in NSCLC, $237.08{\pm}145.15U/L$ in SCLC, $126.54{\pm}95.72U/L$ in non-malignant pulmonary lung disease, and $63.68{\pm}31.66U/L$ in healthy adults. The serum values of the lung cancer groups were significantly higher than those of the control group (p<0.01). Using a cut off value of 188U/L, sensitivity and specificity was 66.4% and 81.9% in NSCLC, and 43.8% and 81.9% in SCLC, respectively. The serum levels of CK 8, 18 and 19 were higher in advanced NSCLC than in early stage disease. Conclusion : The serum levels of CK 8, 18 and 19 may be useful in the diagnosis of NSCLC.

• Korean Journal of Environmental Agriculture
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• v.22 no.3
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• pp.185-191
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• 2003

The mechanism imparting salt tolerance to crop plants remains still unsolved, although soybean has been classified as a susceptible plant to NaCl. To determine optimum parameters on physiological responses for improving sensitivity of salinity in breeding program, soybean (Glycine max Merr., cv. "Gwan-gan") plants were grown in a greenhouse, treated 20 days after emergence for 7 days with NaCl at 0, 30, 60, and 90mM, corresponding to electric conductivity of 1.2, 4.4, 7.3, and 10.4 dS/m, respectively, and assessed 30 days after treatment. Chlorophyll contents were significantly decreased by NaCl ($0.4{\sim}1.0\;mg/g$) compared to control (1.2 mg/g). Photosynthesis rate by NaCl treatment at $0{\sim}90\;mM$ at flowering stage was ranged from 5.0 (control) to $9.6\;{\mu}mol/m^2/s$. Oxygen for respiration was consumed from 5.4 to $9.7\;{\mu}mol/m^2/s$ so that the ratio of $O_2$ (evolution:consumption) was increased with the increase of NaCl, indicating that $O_2$ consumption seems to go beyond $O_2$ evolution. Water potential of leaf at vegetative stage II was ranged from -0.6 to -1.8 MPa and the highest level was observed at mid-day. Water potential by salt stress was decreased with range of $-2.1{\sim}-2.7MPa$ compared to control. Transpiration was decreased from 17% to 20% by NaCl stress. Water vapor diffusing resistance of intercellular air space was affected significantly, increasing up to $16{\sim}24%$ compared to control by NaCl treatment. Salt-treated soybean tended to accumulate $Na^+$, specially in root, with reduced absorption of N, P, $K^+$, $Ca^{2+}$, and $Mg^{2+}$ contents. Free proline content of soybean leaf as affected by different NaCl concentrations was increased 4.2 times ($184{\sim}434\;{\mu}g/g$) more than control. NaCl also increased activities of nitrate reductase and peroxidase by $28{\sim}161%$ and $3{\sim}22%$, respectively. The results show that physiological characteristics of soybean plants during assay were useful as the best parameters of salt stress or salt tolerance test to improve sensitivity in screening and breeding program among cultivars or germplasms.