• Radiation Oncology Journal
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• v.17 no.1
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• pp.1-8
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• 1999

Purpose : Experimental studies have implicated the wild type p53 In cellular response to radiation. Whether altered p53 function can lead to changes in clinical radiocurability remains an area of ongoing study. This study was performed to investigate whether any correlation between change of p53 and outcome of curative radiation therapy in patients with head and neck cancels. Methods : Immunohistochemical analysis with a mouse monoclonal antibody (DO-7) specific for human p53 was used to detect to overexpression of protein in formalin fixed, paraffin-embedded tumor sample from 55 head and neck cancer patients treated with curative radiation therapy (median dose of 7020 cGy) from February 1988 to March 1996 at 51. Mary's Hospital. Overexpression of p53 was correlated with locoregional control and survival using Kaplan-Meier method. A Cox regression multi-variate analysis was peformed that included all clinical variables and status of p53 expression. Results : Thirty-seven (67.2$\%$) patients showed overexpression of p53 by immunohistochemical staining in their tumor. One hundred percent of oral cavity, 70$\%$ of laryngeal, 66.7$\%$ of oropharyngeal, 66.7$\%$ of hypopharyngeal cancer showed p53 overexpression (P=0.05). The status of p53 had significant relationship with stage of disease (P=0.03) and history of smoking (P=0.001). The overexpression of p53 was not predictive of response rate to radiation therapy. The locoregional control was not significantly affected by p53 status. Overexpression of p53 didn't have any prognostic implication for disease free survival and overall survival. Primary site and stage of disease were significant prognostic factors for survival. Conclusions : The p53 overexpression as detected by immunohistochemical staining had significant correlation with stage, primary site of disease and smoking habit of patients. The p53 overexpression didn't have any predictive value for outcome of curative radiation therapy in a group of head and neck cancers.

• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.273-280
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• 2005

Purpose: Cyclin G2 has been reported to be a negative cell-cycle regulator in various cancer tissues. However, the pattern of cyclin G2 expression in gastric cancer is relatively unknown. We investigated the expression of cyclin G2 in gastric cancer tissues and evaluated the clinical significance of its expression. Materials and Methods: Well-preserved gastric cancer tissues were consecutively obtained from 172 patients who underwent gastric cancer operations at Samsung Medical Center between November 1994 and December 1997. Cyclin G2 expression in the tissues was examined immunohistochemically, and the clinicopathological features and prognostic significance according to the expression were analyzed. Results: Of the 172 gastric cancer tissues, cyclin G2 expression was positive in 43 tissues (25.0%). According to the stage, cyclin G2 expression was lower in more advanced stages (P<0.001). Negative expression of cyclin G2 was positively correlated with more advanced depth of tumor invasion (P<0.05), presence of lymph-node metastasis (P<0.05) and presence of lymphatic invasion (P<0.05). The prognosis of the cyclin G2(+) group was significantly better than that of the cyclin G2(-) group (P<0.001). Multivariate analysis revealed that T stage, lymph-node metastasis, distant metastasis, and lymphatic invasion were independent prognostic factors, but the expression of cyclin G2 was not. Conclusion: Cyclin G2 was expressed in 25% of the gastric cancer tissues, and negative expression of cyclin G2 was associated with more advanced tumor progression. Cyclin G2 may be a negative cell-cycle regulator in gastric cancer, and further studies are necessary to elucidate its exact role in the mechanism of carcinogenesis.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.229-240
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• 1999

Background: The impact of the immune response on cancer gene therapy using viral vectors to deliver a "suicide gene" is currently unclear. A vigrous immune response targeted at viral proteins or transgene may enhance the efficacy of tumor destruction and even augment responses to tumor antigens. These responses may involve the release of cytokines and stimulation of tumor specific cytotoxic T-lymphocytes that enhance therapeutic efficacy. On the other hand, a vigorous rapid cellular immune response may destroy cells expressing the therapeutic gene and attenuate the response to therapy. Furthermore, development of neutralizing antibody responses may prevent readministration of virus, a potentially significant limitation. Evaluating the significance of these limitations in animal models and developing solutions are therefore of obvious importance. Methods: After retroviral transduction of mouse mesothelioma cell line(AB12) with Herpes Simplex Virus thymidine kinase (HSVtk) gene in vitro, subcutaneous flank tumors were established. To study the effect of intact immune system on efficacy of tumor erradication, the ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Balb/c mice, immunodeficient Balb/c-nude and SCID mice, and Balb/c mice immunosuppressed with cyclosporin. Results: Ganciclovir treatment resulted in greater inhibition of tumor growth in Balb/c mice compared with immunodeficient Balb/c-nude mice and SCID mice(in immunodeficient mice, there were no growth inhibition by ganciclovir treatment). Ganciclovir treatment resulted in greater inhibition of tumor growth in noncyclosporin (CSA) treated Balb/c mice compared with CSA treated Balb/c mice. On day 8, mean ganciclovir-treated tumor volume were 65% of control tumor volume in Balb/c mice versus 77% control tumor volume in CSA-treated Balb/c mice. This effect was still evident during therapy (day 11 and 13). On day 13, non-CSA treated tumor volume was 35% of control tumor volume versus 60% of control tumor volume in CSA treated Balb/c mice. Duration of expression of HSVtk was not affected by the immunosuppression with CSA. Conclusion: These results indicate that the immune responses against retrovirally transduced cells enhance the efficacy of the HSVtk/ganciclovir system. These findings have important implications for clinical trials using currently available retrovirus vectors as well as for future vector design.

• Clinical and Experimental Pediatrics
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• v.51 no.9
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• pp.971-976
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• 2008

Purpose : Surveillance for detecting and managing latent tuberculosis infection (LTBI) is a key component of tuberculosis control. The classic surveillance tool, the tuberculin skin test (TST), may have some limitations when used in the Bacillus Calmette-$Gu{\acute{e}}rin$ (BCG)-vaccinated population. The object was to perform a blood test $QuantiFERON^{(R)}$-TB Gold In Tube (QFT-G IT) based on the detection of interferon-$\gamma$ ($IFN-{\gamma}$) released by T cells in response to Mycobacterium tuberculosis-specific antigens, and to compare the efficacy of this new diagnostic tool for LTBI with that of TST. Methods : For six months, between October 1, 2006 and April 30, 2007, data were collected from 111 patients under 15 years of age at Severance Children's Hospital. TST and QFT-G IT tests were performed with children with or without contact histories of tuberculosis. In addition to these tests, we examined comparative data from 29 adults who had tuberculosis, to detect false negative rates in the QFT-G IT method. Results : Thirty-three children had household contact histories. In this group, 15% and 42% of cases were found to be positive using the QFT-G IT assay and TST, respectively. Agreement was low between these two tests (${\kappa}=0.39$). In the adult active tuberculosis group, the QFT-G IT false negative rate defined as a positive culture and a negative QFT-G IT result was 12.5%. Conclusion : In diagnosing LTBI in children, the usefulness of a whole-blood $IFN-{\gamma}$ assay employing TB-specific antigens will be revealed only by examining additional longitudinal clinical data; this study serves as a starting point in that process.

• Journal of Life Science
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• v.30 no.8
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• pp.701-707
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• 2020

Gene editing technology using the clustered regularly interspaced short palindromic repeat (CRISPR) and the CRISPR associated protein (Cas)9 has been highly anticipated in developing breeding techniques. In this study, we discuss gene scissors as a tool for silkworm molecular breeding through analysis of Bombyx mori Kynurenine 3-Monooxygenase (BmKMO) gene editing using the CRISPR/Cas9 system and analysis of generational transmission through mutagenesis and selective crossing. The nucleotide sequence of the BmKMO gene was analyzed, and three guide RNAs (gRNAs) were prepared. Each synthesized gRNA was combined with Cas9 protein and then analyzed by T7 endonuclease I after introduction into the BM-N silkworm cell line. To edit the silkworm gene, K1P gRNA and Cas9 complexes were subsequently microinjected into the silkworm embryos; the hatching rate was 18% and the incidence of mutation was 60%. The gene mutation was verified in the heterozygous G0 generation, but no phenotypic change was observed. In homozygotes generated by self-crossing, a mutant phenotype was observed. These results suggest that silkworm molecular breeding using the CRISPR/Cas9 system is possible and could be an effective way of shortening the time required.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.24-33
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• 2016

Mucopolysaccharidosis type VI (MPS VI) is a rare disease caused by the mutation of ARSB with prevalence range from 1/5,000 in northeast Brazil to 1/2,057,529 births in Czech Republic. In Asia, there is only one published figure in Taiwan of about 1/833,000 births. The exact prevalence in the Korean population is unknown, but we estimated the incidence of MPS VI is about 0.03/100,000 live births. Enzyme replacement therapy (ERT) with recombinant human Arylsulfatase B (rhASB) is a modality for the treatment of MPS VI that reduces the excretion of urine glycosaminoglycan (GAG) and improves joint motion, pulmonary function, and endurance. We presented the clinical features, molecular analysis and outcome of ERT in three Korean MPS VI patients. All patients had the typical characteristic clinical features of MPS IV. Short stature, dysostosis multiplex, corneal opacity and valvular heart disease were found at first presentation, while restrictive lung disease and carpal tunnel syndrome developed later in all patients. Molecular analysis demonstrated novel missense and nonsense mutation in the patients, including p.Ile 67Ser, p.Gly328Arg, $p.Arg191^*$, p.Asp352Asn, and p.Gly17Asp. After ERT, urine GAG was decreased in all patients. Skeletal involvement, corneal opacity, heart valve abnormalities and pulmonary function were not improved with ERT, but it had a better outcome on regarding joint motion and endurance. One patient underwent allogeneic bone marrow transplantation (BMT) prior to ERT, but their clinical response was not improved much after BMT. This study demonstrates clinical phenotypes and molecular analysis of the severe form of MPS VI in Korean patients.

• Journal of Chest Surgery
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• v.32 no.4
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• pp.333-340
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• 1999

Background: Plasminogen activator inhibitor-1(PAI-1) is known as the primary physiological inhibitor of tissue-type plasminogen activator(t-PA) in the plasma, and is present within the atherosclerotic vessels. Increased plasma levels of PAI-1 are one of the major disturbances of the hemostatic system in patients with diabetes and/or hypertension, and may have multiple interrelations with the important risk factors in the development of atherosclerosis. This study was performed to determine whether altered gene expression of PAI-1 occurs within the arterial wall, and thereby potentially contributing to the increase of cardiovascular risks associated with diabetes and/or hypertension. Material and Method: The aortic vascular smooth muscle cells of the rat were exposed to 22 mM glucose, angiotensin II, and insulin increased PAI-1 mRNA expression with the use of Northern blotting were examined. Also examined were the effects of 22 mM glucose, angiotensin II and insulin on the growth of the rat's aortic smooth muscle cells by using MTT assay. Result: Twenty-two mM glucose treatment increased the PAI-1 mRNA expression in a time- and dose-dependent manner. Aniotensin II treatment synergistically increased the glucose-induced PAI-1 mRNA expression. In contrast, addition of insulin attenuated the increase of 22 mM glucose and angiotensin II induced PAI-1 mRNA expression. Furthermore, treatment of 22 mM glucose, angiotensin II and insulin resulted in a significant increase in cell numbers. This study demonstrated that 22 mM glucose and angiotensin II have a synergistic effect in stimulating the PAI-1 mRNA expression and in the cell growth of the rat's aortic smooth muscle cells. Conclusion: Elevation of glucose and angiotensin II may be important risk factors in impairing fibrinolysis and developing atherosclerosis in diabetic patients.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.8
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• pp.1197-1203
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• 2013

This study investigated the effects of endurance exercise and ginsenoside $Rb_1$ on AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K) protein expression and glucose uptake in the skeletal muscle of rats. A total of 32 rats were randomly divided into four groups: CON (Control group, n=8), Ex (Exercise group; 25 m/min for 1 h, 6 days/week, 2 weeks, n=8), $Rb_1$ (Ginsenoside $Rb_1$ group; n=8), and $Rb_1/Ex$ ($Rb_1$+Exercise group, n=8). The $Rb_1$ and $Rb_1/Ex$ groups were incubated in ginsenoside $Rb_1$ (KRBP buffer, $100{\mu}g/mL$) for 60 min after a 2-week experimental treatment. After 2 weeks, the expression of phosphorylated $AMPK{\alpha}$ $Thr^{172}$, total $AMPK{\alpha}$, the p85 subunit of PI3K, pIRS-1 $Tyr^{612}$, and pAkt $Ser^{473}$ were determined in the soleus muscle. Muscle glucose uptake was measured using 2-deoxy-D-[$^3H$] glucose in epitroclearis muscle. Muscle glucose uptake was significantly higher in the three experimental groups (Ex, $Rb_1$, $Rb_1/Ex$) compared to the CON group (P<0.05). The expression of $tAMPK{\alpha}$ and $pAMPK{\alpha}$ $Thr^{172}$ was significantly higher in the Ex, $Rb_1$, and $Rb_1/Ex$ groups compared to the CON group (P<0.05). The expression of pAkt $Ser^{473}$ was significantly higher in the $Rb_1$ group compared to the CON and EX groups. However, the expression of pIRS-1 $Tyr^{612}$ and the p85 subunit of PI3K were not significantly different between the four groups. Overall, these results suggest that ginsenoside $Rb_1$ significantly stimulates glucose uptake in the skeletal muscle of rats through increasing phosphorylation in the AMPK pathway, similar to the effects of exercise.

• Investigative Magnetic Resonance Imaging
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• v.9 no.1
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• pp.30-35
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• 2005

Purpose : The purpose of this study is to observe the blood oxygen level dependent (BOLD) contrast changes due to the reaction of human brain at a gustatory sense in response to a salty-taste stimulation. Materials and Methods : Twelve healthy, non-smoking, right-handed male subjects (mean age: 25.6, range: 23-28 years) participated in this salty-taste stimulus functional magnetic resonance (fMRI) study. MRI scans were performed with 1.57 GE Signa, using a multi-slice GE-EPI sequence according to a blood-oxy-gen-level dependent (BOLD) experiment paradigm. Scan parameters included matrix size $128\times128$, FOV 250 mm, TR 5000 msec, TE 60 msec, TH/GAP 5/2 mm. Sequential data acquisitions were carried out for 42 measurements with a repetition time of 5 sec for each taste-stimulus experiments. Analysis of fMRI data was carried out using SPM99 implemented in Matlab. NaCl solution $(3\%)$ was used as a salty stimulus. The task paradigm consisted of alternating rest-stimulus cycles (30-second rest, 15-second stimulus) for 210 seconds. During the stimulus period, NaCl-solution was presented to the subject's mouth through plastic tubes as a bolus of delivered every 5 sec using -processor controlled auto-syringe pump. Results : Insula, frontal opercular taste cortex, amygdala and orbitofrontal cortex (OFC) were activated by a salty-taste stimulation $(NaCl,\;3\%)$ in the fMRI experiments. And dosolateral prefrontal cortex (DLPFC) was also significantly responded to salty-taste stimuli. Activation areas of the right side hemisphere were more superior to the left side hemisphere. Conclusion : The results of this study well correspond to the fact that both insula, amygdala, OFC, DLPFC areas are established as taste cortical areas by neuronal recordings in primates. Authors found that laboratory-developed auto-syringe pump is suitable for gustatory fMRI study. Further research in this field will accelerate to inquire into the mechanism of higher order gustatory process.

• Journal of radiological science and technology
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• v.32 no.3
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• pp.325-334
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• 2009

Purpose : This study was conducted to assess how effective the permeability ratio and relative cerebral blood volume ratio are to tumor through perfusion MRI by measuring and reflecting the grade assessment and differential diagnosis and the permeability and relative cerebral blood volume of contrast media plunged from blood vessel into organ due to breakdown of blood-brain barrier in cerebral. Subject and Method : Subject of study was 29 patients whose diagnosis were confirmed by biopsy after surgery and 550 (11 slice$\times$50 image) perfusion MRI were used to make image of relative cerebral blood volume with the program furnished on instrument. The other method was to transmit to private computer and the image analysis was made additionally by making image of relative cerebral blood volume-reformulated singular value decomposition, rCBV-rSVD and permeability using IDL.6.2. In addition, Kruskal-wallis test tonggyein non numerical average by a comparative analysis of brain tumors Results : The rCBV ratio (Functool PF; GE Medical Systems and IDL 6.2 program by analysis) and permeability ratio of tumors were as follows; high grade glioma(n=4), (14.75, 19.25) 13.13. low grade astrocytoma(n=5) (14.80, 15.90) 11.60, glioblastoma(n=5) (10.90, 18.60), 22.00, metastasis(n=6) (11.00, 15.08). 22.33. meningioma(n=6) (18.58, 7.67), 5.58. oliogodendroglioma(n=3) (23.33, 16.33, 15.67. Conclusion : It was not easy to classify the grade with the relative cerebral blood volume ratio measured by using the relative cerebral blood image by type of tumors, however, permeability ratio measured by permeability image revealed that the higher the grade of tumor, the higher the measured permeability ratio, showing the assessment of tumor grade is more effective to differential diagnosis.