• Biomolecules & Therapeutics
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• v.22 no.2
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• pp.114-121
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• 2014

Refractoriness of acute myeloid leukemia (AML) cells to chemotherapeutics represents a major clinical barrier. Suicide gene therapy for cancer has been attractive but with limited clinical efficacy. In this study, we investigated the potential application of herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) based system to inhibit chemoresistant AML cells. We first generated Ara-C resistant K562 cells and doxorubicin-resistant THP-1 cells. We found that the HSV-TK/GCV anticancer system suppressed drug resistant leukemic cells in culture. Chemoresistant AML cell lines displayed similar sensitivity to HSV-TK/GCV. Moreover, HSV-TK/GCV killing of leukemic cells was augmented to a mild but significant extent by all-trans retinoic acid (ATRA) with concomitant upregulation of Connexin 43, a major component of gap junctions. Interestingly, HSV-TK/GCV killing was enhanced by expression of vesicular stomatitis virus G glycoprotein (VSV-G), a fusogenic membrane protein, which also increased leukemic cell fusion. Co-culture resistant cells expressing HSV-TK and cells stably transduced with VSV-G showed that expression of VSV-G could promote the bystander killing effect of HSV-TK/GCV. Furthermore, combination of HSV-TK/GCV with VSV-G plus ATRA produced more pronounced antileukemia effect. These results suggest that the HSV-TK/GCV system in combination with fusogenic membrane proteins and/or ATRA could provide a strategy to mitigate the chemoresistance of AML.

• Molecules and Cells
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• v.21 no.1
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• pp.104-111
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• 2006

Gene therapy with nonviral vectors using the suicide gene/prodrug activating system of herpes simplex virus type-1 thymidine kinase (HSV1-TK)/ganciclovir (GCV) is inefficient in killing malignant tumor cells due to two major factors: (a) an unsatisfactory bystander effect; (b) short-lived expression of the protein. To study the capacity of the protein transduction domain (PTD) of HIV-1 TAT protein to enhance HSV1-TK/GCV cancer gene therapy, we constructed three fusion proteins TAT-TK, TK-TAT and TK. TAT-TK retained as much enzyme activity as TK, whereas that of TK-TAT was much lower. TAT-TK can enter HepG2 cells and much of it is translocated to the nucleus. The transduced HepG2 cells are killed by exogenously added GCV and have bystander effects on untransduced HepG2 cells. Most importantly, the introduced recombinant protein is stable and remains functional for several days at least, probably because nuclear localization protects it from the cytoplasmic degradation machinery and provides access to the nuclear transcription machinery. Our results indicate that TAT fusion proteins traffic intercellularly and have enhanced stability and prodrug cell killing activity. We conclude that TAT has potential for enhancing enzyme prodrug treatment of liver cancers.

• Journal of Digital Convergence
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• v.19 no.6
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• pp.355-362
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• 2021

This study was attempted to examine the effectiveness of mobile-based military WithYou programs. The research design was a quasi-experimental study with one group pretest-posttest design. Data were collected from 17 December to 23 December 2020. 42 and 37 members of the Air base in City C participated in the pretest and posttest, respectively. A video education program developed to inspire bystander intervention efficacy and the intention of helping peers and strangers was provided on mobile. The data collected before and after attending the program were analyzed using descriptive statistics and t-test. The results showed that mobile-based military WithYou program was effective in increasing the intention to help friends and others. Attempts to develop and apply educational content using mobile devices for military personnel will be meaningful.

• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.587-595
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• 1998

Background: Recombinant adenovirus hold promise as vectors to carry therapeutic genes for several reasons: 1) they can infect both dividing and non-dividing cells; 2) they have the ability to directly transduce tissues in vivo; 3) they can easily be produced in high titer; and 4) they have an established record of safety as vaccination material. However, one of the major limitation in the use of adenoviruses is that transgene expression is quite short because adenovirusees insert their DNA genome episomally rather than by chromosomal integration, and an immune response against the virus destroys cells expressing the therapeutic gene. Since sodium butyrate has been reported to induce adenovirus-mediated gene expression, we hypothesized that treatment of tumor cells, transduced with herpes simples virus thymidine kinase(HSVtk) gene using adenoviral vector, with butyrate could augment the effect of gene therapy. Methods: We transduced HSVtk gene, driven by the cytomegalovirus promoter, into REN cell line(human mesothelioma cell line). Before proceeding with the comparison of HSVtk/ganciclovir mediated bystander killing, we evaluated the effect of butyrate on the growth of tumor cells in order to rule out a potential antitumor effect of butyrate alone, and also on expression of HSVtk gene by Western blot analysis. Then we determined the effects of butyrate on bystander-mediated cell killing in vitro. Results: There was no inhibition of growth of cells exposed to butyrate for 24 hours at a concentration of 1.5mM/L. Toxic effects were seen when the concentration of butyrate was greater than 2.0mM/L. Gene expression was more stable and bystander effect was augmented by butyrate treatment of a concentration of 1.5mM/L. Conclusion: These results provide evidence that butyrate can augment the efficiency of cell killing with HSVtk/GCV system by inducing transgene expression and may thus by a promising new approach to improve responses in gene therapy using adenoviral vectors.

• Clinical and Experimental Pediatrics
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• v.46 no.6
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• pp.541-547
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• 2003

Purpose : Gap junction intercellular communication(GJIC) is an important mechanism of the bystander effect in herpes simplex thymidine kinase/ganciclovir(HSVtk/GCV) gene therapy Therefore, we attempted to enhance the bystander effect in vitro by exogenous overexpressing connexin 37(Cx37) in cells to increase GJIC. Methods : NIH3T3 cells were transfected with the Cx37 and HSVtk gene or the HSVtk gene alone by the calcium phosphate method, and we detected their expression from these cells by RT-PCR. GCV-mediated cytotoxicity and the bystander effect of each transfectant was then assessed and compared. Results : Cells transfected with HSVtk became sensitive to low concentration of GCV. We found significantly increased cytotoxicity in HSVtk/GCV gene therapy after introduction of the HSVtk and Cx37 genes together compared with the cytotoxicity seen after introduction of the HSVtk gene in vitro. Co-expression of the HSVtk and Cx37 genes potentiates HSVtk/GCV gene therapy through the bystander effect. Conclusion : These results indicated that the increase of GJIC using Cx37 have potentiated the bystander effect of HSVtk/GCV therapy, and may be a new approach to improve response in suicidal cancer gene therapy.

• The Journal of Korean Academic Society of Nursing Education
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• v.16 no.2
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• pp.339-346
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• 2010

Purpose: Bystander cardiopulmonary resuscitation (CPR) improves survival. However, there have been few studies on the performance of bystander CPR in Korea. This study was done to identify the reasons for being unwilling to perform CPR, and to investigate the factors associated with performing CPR on a stranger in an emergency situation. Method: The participants in this study were 444 local residents. Data were collected by using self-reported questionnaires from May 1 to June 30, 2010. For data analysis, descriptive statistics and multiple logistic regression were performed using SAS version 9.1. Result: Only 32.2% of respondents reported being willing to perform CPR on a stranger. The major reason for not being willing to perform CPR on a stranger was "have no confidence to perform CPR well". From multiple logistic regression analysis, statistically significant predictors of CPR performance on a stranger were found to be a higher educational level (OR=6.11, 95% CI 1.46-25.52), neighbors with angina pectoris or myocardial infarction (OR=6.65, 95% CI 3.93-11.24), and having confidence of performing CPR (OR=3.02, 95% CI1.78-5.14). Conclusion: CPR education (including automatic external defibrillator) should be offered to family members and neighbors. In addition, the Good Samaritan Law must be given wider publicity at the national level.

• Nuclear Engineering and Technology
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• v.40 no.7
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• pp.551-560
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• 2008

Radiation has stochastic aspects in its generation, its choice of interaction mode during traveling in media, and its impact on living bodies. In certain circumstances, like in high dose environments resulting from low-LET radiation, the variance in its impact on a target volume is negligible. On the contrary, in low dose environments, especially when they are attributed to high-LET radiation, the impact on the target carries with it a large variance. This variation is more significant for smaller target volumes. Microdosimetric techniques, which have been developed to estimate the distribution of radiation energy deposited to cellular and subcellular-sized targets, contrast with macrodosimetric techniques which count only the average value. Since cells and DNA compounds are the critical targets in human bodies, microdosimetry, or dose estimation by microscopic approach, helps one better analyze the biological effects of radiation on the human body. By utilizing microbeam systems designed for individual cell irradiation, scientists have discovered that human cells exhibit radiosensitive reactions without being hit themselves (bystander effect). During the past 10 or more years, a new therapeutic protocol using discontinuous multiple micro-slit beams has been investigated for its clinical application. It has been suggested that the beneficial bystander effect is the essence of this protocol.

• Safety and Health at Work
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• v.14 no.1
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• pp.131-134
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• 2023

The aim was to describe out-of-hospital cardiac arrest (OHCA) occurring in the workplace of a large emergency network, and compare the evolution of their management in the last 15 years. A retrospective study based on data from the Northern Alps Emergency Network compared characteristics of OHCA between cases in and out the workplace, and between cases occurring from January 2004 to December 2010 and from January 2011 to December 2017. Among the 15,320 OHCA cases included, 320 occurred in the workplace (2.1%). They were more often in younger men, and happened more frequently in an area with access to public defibrillation, had more often a shockable rhythm, had a cardiopulmonary resuscitation started by a bystander more frequently, and had a better outcome. Cardiopulmonary resuscitation started by a bystander was the only chain of survival link that improved for cases occurring after December 2010. Workplace OHCA seems to be managed more effectively than others; however, only a slight survival improvement was observed, suggesting that progress is still needed.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.11 no.4
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• pp.1540-1546
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• 2010

In order to report characteristics of out-of-hospital cardiac arrest patient in whom 119 rescuers used prehospital care by Paramedic's Reports. 1,016 out-of-hospital cardiac arrest patients were transferred to hospitals by 119 rescuers between January 1st and December 31st, 2008. Prehospital reports of 983 cardiac arrest patients by 119 were analyzed. Shockable rhythm with AED use was 20.3%(VF 18.4%, VT 1.9%), then 66.5% of shockable cardiac arrest patients was resuscitated by AED. Bystander basic life support was 14.8%. There were significant differences in the recurrent survival rates between shockable rhythm and non-shockable rhythm(13.0% vs 2.0%,7.4%, p=0.000). There was also significant differences in the recurrent survival rates between adequacy rate of AED(21.6% vs 2.4%, p=0.000). But there was no significant differences in the recurrent survival rates between done bystander CPR and none(9.0% vs 5.5%, p=0.10). The performance of bystander CPR and usage of AED, and appropriate CPR done by 119 rescuers were unsatisfactory by paramedic's reports. To improve the adequacy of Basic life Support and to increase the performance on Advanced Life Suppport, we must challenge to develop the emergency medical systems.

• Journal of Digital Convergence
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• v.11 no.9
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• pp.229-238
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• 2013

Out-of-hospital cardiac arrest is a major public health problem in Korea. The survival rate to discharge remains at approximately 3.5% and only 1% have good neurological function. To increase the survival rate, prehospital care should restore spontaneous circulation. The purpose of this study was to analyze the factors associated with return of spontaneous circulation(ROSC) after out-of-hospital cardiac arrest. Data used for this study were collected from KCDC Out-of-Hospital Cardiac Arrest Surveillance 2009. As for the results of decision tree analysis, it is clear that prehospital CPR, cardiac arrest witness, activity, past history(cancer/heart disease/stroke), place, bystander CPR, response time, age, etc are significant contributing factors in ROSC. Among 16 cardiac arrest types from decision tree classification, the ROSC rate of type 1 is the highest(29.6%). Also notable is the fact that bystander CPR was strongly correlated with ROSC of patents with cardiac arrest occurring in non-public places. Community resources should be concentrated on increasing bystander CPR and early prehospital emergency care.