• Title/Summary/Keyword: radiation/induce

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Radiosensitization Effect of Overexpression of Adenovirus-mediated SIRT6 on A549 Non-small Cell Lung Cancer Cells

  • Cai, Yong;Sheng, Zhao-Ying;Liang, Shi-Xiong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7297-7301
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    • 2014
  • Objective: To explore the radiosensitization effect of overexpression of silent information regulator 6 (SIRT6) on A549 non-small cell lung cancer (NSCLC) cells. Methods: Adenovirus vector Ad-SIRT6 causing overexpression of SIRT6 was established. Western blotting and MTT assay were adopted to detect the level of SIRT6 protein and the inhibitory rate of A549 cell proliferation after different concentrations of adenovirus transduction (0, 25, 100, 200, and 400 pfu/cell) for 24 h. Control group, Ad-null group and Ad-SIRT6 group were designed in this experiment and virus concentration of the latter two groups was 200 pfu/cell. Colony formation assays were employed to test survival fraction (SF) of the 3 groups after 0, 2, 4, 6, 8, 10 X-ray irradiation. Flow cytometry was used to detect the status of cell cycle of 3 groups after 48 h of 4Gy X-ray irradiation and Western blotting was used to determine the expression of apoptosis-related genes of 3 groups after 48 h of 4GyX-ray irradiation. Results: In the range of 25~400 pfu/cell, the inhibitory rate of A549 cell proliferation increased as adenovirus concentration raised. The inhibitory rates under the concentrations of 0, 25, 100, 200, and 400 pfu/cell were 0%, $4.23{\pm}0.34%$, $12.7{\pm}2.57%$, $22.6{\pm}3.38%$, $32.2{\pm}3.22%$, $38.7{\pm}4.09%$ and $47.8{\pm}5.58%$ and there were significantly differences among groups (P<0.05). SF in Ad-SIRT6 group was lower than Ad-null and control groups after 4~10Gy X-ray irradiation (P<0.05) and the sensitization enhancement ratio (SER) was 1.35 when compared with control group. Moreover, after 48 h of 4Gy X-ray irradiation, there appeared a significant increase in G1-phase cell proportion, upregulated expression of the level of apoptosis-promoting genes (Bax and Cleaved caspase-3), but a obvious decline in S-phase and G2-phase cell proportion and a significant decrease of the level of apoptosis-inhibiting gene (Bal-2) in the Ad-SIRT6 group (P<0.05). Conclusion: The over-expression of adenovirus-mediated SIRT6, which has radiosensitization effect on A549 cells of NSCLC, can inhibit the proliferation of A549 cells and cause G0/G1 phase retardation as well as induce apoptosis of cells.

Design of the Detector Head for Single Photon Detection in Breast Cancer Diagnosis and Its Performance Evaluation (유방암진단에서의 단일광자검출을 위한 검출기 전단부의 설계와 성능평가)

  • Kim, Kwang-Hyun;Cho, Gyu-Seong;Chung, Woon-Kwan
    • Journal of Radiation Protection and Research
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    • v.28 no.4
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    • pp.263-270
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    • 2003
  • Monte Carlo simulation has been peformed to induce optimized parameters of the detector head of gamma camera for the diagnosis of breast cancer and to evaluate it under the diagnosis condition of the breast cancer. For the simulation, we used Tungsten collimator, having a lattice structured array with holes of $3mm{\times}3mm$ and septal thickness of 0.25 mm, which are corresponding to the pixellated photosensor. For driving optimum parameters we used Trade-Offs procedure between the geometric efficiency and the spatial resolution, varying the detector head components. In order to pre-evaluate the performance of the optimized detector head, we assumed diagnosis condition that the breast tumor is located in the middle of phantom with various sizes and its location is 25 mm from the collimator surface, considering background count caused by radiation sources from other organs. It was shown that the performance of the optimized detector head can be degraded according to the breast cancer size and the background count under real diagnosis conditions of breast cancer. Therefore, it is concluded that the spatial resolution, which is used as an indicator to distinguish the various sizes of breast cancer and is dependent on the characteristic of the detector head, appears to be meaningless in early diagnosis of the breast cancer.

Calculation of Primary Electron Collection Efficiency in Gas Electron Multipliers Based on 3D Finite Element Analysis (3차원 유한요소해석을 이용한 기체전자증폭기의 1차 전자수집효율의 계산)

  • Kim, Ho-Kyung;Cho, Min-Kook;Cheong, Min-Ho;Shon, Cheol-Soon;Hwang, Sung-Jin;Ko, Jong-Soo;Cho, Hyo-Sung
    • Journal of Radiation Protection and Research
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    • v.30 no.2
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    • pp.69-75
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    • 2005
  • Gas avalanche microdetectors, such as micro-strip gas chamber (MSGC), micro-gap chamber (MGC), micro-dot chamber (MDOT), etc., are operated under high voltage to induce large electron avalanche signal around micro-size anodes. Therefore, the anodes are highly exposed to electrical damage, for example, sparking because of the interaction between high electric field strength and charge multiplication around the anodes. Gas electron multiplier (GEM) is a charge preamplifying device in which charge multiplication can be confined, so that it makes that the charge multiplication region can be separate from the readout micro-anodes in 9as avalanche microdetectors possible. Primary electron collection efficiency is an important measure for the GEM performance. We have defined that the primary electron collection efficiency is the fractional number of electron trajectories reaching to the collection plane from the drift plane through the GEM holes. The electron trajectories were estimated based on 3-dimensional (3D) finite element method (FEM). In this paper, we present the primary electron collection efficiency with respect to various GEM operation parameters. This simulation work will be very useful for the better design of the GEM.

Bioassay in BALB/c mice exposed to low dose rate radiation (저선량율 방사선 조사한 BALB/c 마우스에서의 영향평가)

  • Kim, Sung-Dae;Gong, Eun-Ji;Bae, Min-Ji;Yang, Kwang-Mo;Kim, Joong-Sun
    • Journal of Radiation Protection and Research
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    • v.37 no.3
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    • pp.159-166
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    • 2012
  • The present study was performed to investigate the toxicity of low-dose-rate irradiation in BALB/c mice. Twenty mice of each sex were randomly assigned to four groups of five mice each and were exposed to 0 (sham), 0.02, 0.2, or 2 Gy, equivalents to low-dose-rate irradiation to 3.49 $mGy{\cdot}h^{-1}$. Urine, blood, and blood biochemistry were analyzed, and organ weight was measured. The low-dose-rate irradiation did not induce any toxicologically significant changes in mortality, clinical signs, body weight, food and water consumption, urinalysis, and serum biochemistry. However, the weights of reproductive organs including the testis, ovary, and uterus decreased in a dose-dependent manner. Irradiation at 2 Gy significantly decreased the testis, ovary, and uterus weights, but did not change the weights of other organs. There were no adverse effects on hematology in any irradiated group and only the number of neutrophils increased dose dependently. The low-dose-rate irradiation exposure did not cause adverse effects in mice at dose levels of 2 Gy or less, but the reproductive systems of male and female mice showed toxic effects.

Intratumoral Administration of Dendritic Cells Combined with Hyperthermia Induces Both Local and Systemic Antitumor Effect in Murine Tumor Models (온열 요법 후 종양 내 주입한 수지상 세포의 국소 및 원격 항종양 효과)

  • Kwon Byung-Hyun;Kim Won-Taek;Kim Young-Kan;Kim Dong-Won
    • Radiation Oncology Journal
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    • v.24 no.1
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    • pp.51-57
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    • 2006
  • Puroose: We examined whether intratumoral (i.t.) administration of dendritic cells (DCs) into a treated tumor could induce local and systemic antitumor effects in a mouse tumor model. Methods and Materials: C57BL/6 mice were inoculated s.c. in the right and left thighs with MCA-102 fibrosarcoma cells on day 0 and on day 7, respectively. On day 7, the tumors (usually 6 mm in diameter) on the right thigh were heated by immersing the tumor-bearing leg in a circulating water bath at $43^{\circ}C$ for 30 min; thereafter, the immature DCs were i.t administered to the right thigh tumors. This immunization procedure was repeated on days 7, 14 and 21. The tumors in both the right and left thighs were measured every 7 days and the average sizes were determined by applying the following formula, tumor $size=0.5{\times}(length+width)$. Cytotoxicity assay was done to determine tumor-specific cytotoxic T-lymphocyte activity. Results: Hyperthermia induced apoptosis and heat shock proteins (HSPs) in tumor occurred maximally after 6 hr. For the local treated tumor, hyperthermia (HT) alone inhibited tumor growth compared with the untreated tumors (p<0.05), and furthermore, the i.t. administered DCs combined with hyperthermia (HT + DCs) additively inhibited tumor growth compared with HT alone (p<0.05). On the distant untreated tumor, HT alone significantly inhibited tumor growth (p<0.05), and also HT + DCs potently inhibited tumor growth (p<0.001); however, compared with HT alone, the difference was not statistically significant. In addition, HT + DCs induced strong cytotoxicity of the splenocytes against tumor cells compared to DCs or HT alone. Conclusion: HT + DCs induced apoptosis and increased the expression of HSPs, and so this induced a potent local and systemic antitumor response in tumor-bearing mice. This regimen may be beneficial for the treatment of human cancers.

Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis

  • Lim, Chae Jin;Lee, Yong-Moon;Kang, Seung Goo;Lim, Hyung W.;Shin, Kyong-Oh;Jeong, Se Kyoo;Huh, Yang Hoon;Choi, Suin;Kor, Myungho;Seo, Ho Seong;Park, Byeong Deog;Park, Keedon;Ahn, Jeong Keun;Uchida, Yoshikazu;Park, Kyungho
    • Biomolecules & Therapeutics
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    • v.25 no.5
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    • pp.511-518
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    • 2017
  • Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by $SA-{\beta}-gal$ staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.

DEVELOPMENTAL DENTAL COMPLICATIONS AFTER ANTICANCER THERAPY IN CHILDREN (항암 치료를 받은 아동의 치아 발육 장애)

  • Kim, Min-Jeong;Lee, Hyung-Sook;Kim, Shin;Jeong, Tae-Sung
    • Journal of the korean academy of Pediatric Dentistry
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    • v.36 no.4
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    • pp.607-612
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    • 2009
  • The malignant tumor in childhood is one of the main causes of children s death due to disease. The traditional treatment for the malignancy is known for the radiation therapy and the chemical therapy or both. However, the treatments tend to induce intraoral complications. Different from adults, almost all children on cancer therapy are expected to have dental complications, because their permanent teeth are on the developmental stage. The degree of dental complication depends on the patient's age, type of chemical and other factors-radiation dose and frequency. In this report, 3 children who had experienced the anti-cancer therapy on their age between 1 and 4 years were selected and dental complications were examined. The children have chance for the various oral complications including the developmental problems such as agenesis, microdontia and hypoplasia of the teeth. Therefore, it's important to understand the side-effects of anticancer therapy during the permanent teeth had been developmental stage in young patients. Also, oral health care specialists, including pediatric and hospital dentist can support the oncology team by providing basic oral care, implementing oral care protocols, delivering emergency dental treatment undergoing anticancer treatment.

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Evaluation of Phototoxicity for Cosmetics and Alternative Method (화장품 광독성 평가와 동물대체시험법)

  • Lee, Jong-Kwon;Sin, Ji-Soon;Kim, Jin-Ho;Eom, Jun-Ho;Kim, Hyung-Soo;Park, Kui-Lea
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.31 no.3 s.52
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    • pp.245-251
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    • 2005
  • Safety is one of the key issue in the regulation of cosmetics. Cosmetic Act deals with it in Korea. The guidance for the testing cosmetic ingredients and their safety evaluation are prepared by Korea Food and Drug Administration. Ultraviolet radiation could Induce skin damage, edema, erythema, photoaging, immune dysfunction and skin cancer. Ultraviolet radiation is classified as Group 2A(probably carcinogenic to humans) by International Agenry for Reaserch on Cancer(IARC). The in vitro methodologies for evaluating the toxic potential of ingredients reported in the literature have not yet been sufficiently validated for use in areas other than the study for mutagenicity/genotoxicity, for pre-screening for severe irritancy, for screening of phototoxicity and for evaluating the percutaneous absorption. The 3T3 neutral red uptake photoxicity test (3T3 NRU PT) was accepted as OECD toxicity guideline in 2002. The 3T3 NRU PT is an in vitro method based on a comparison of the cytotoxicitv of a chemical when tested in the presence and in the absence of exposure to a non-cytotoxic dose of UVA/visible light.

Radio-sensitivity of Human Colorectal Cancer Cell is Regulated by Potassium Cyanate (Potassium cyanate에 의해 조절되는 사람 대장암 세포의 방사선 감수성 변화)

  • Yang, Eun Ju;Chang, Jeong Hyun
    • Journal of the Korean Society of Radiology
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    • v.13 no.1
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    • pp.125-132
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    • 2019
  • Potassium cyanate (KCN) is an inorganic reagent and can induce the post-translation carbamylation of proteins. The carbamylated reaction in the body is involved in cell death in various diseases. According the results in our previous study, KCN enhances the radiosensitivity of human colorectal cancer cell line, HCT 116 cells. However, it was not enough to confirm the mechanism that KCN works in these cells. To determinated the mechanisms of KCN in the cells with increased radiosensitivity, HCT 116 cells were treated KCN with low-dose gamma-radiation. And then, we examined alteration of the cell cycle, cell proliferation, cytokine level and the activation of cell signaling protein. As a result, cell cycle arrest and cell death were induced by the activation of caspase-3 and PARP in the irradiated cells with KCN treatment. These changes of the irradiated cell with KCN treatment were induced by the release of $TNF-{\alpha}$ via $NF-{\kappa}B$ activation. In conclusions, enhanced radio-sensitivity mediated by KCN induced cell death and it occurs by $NF-{\kappa}B$-dependent $TNF-{\alpha}$ production.

The Effects of Simultaneous Pulmonary Rehabilitation during Thoracic Radiotherapy in the Treatment of Malignant Diseases

  • Choi, Myeong Geun;Lee, Hyang Yi;Song, Si Yeol;Kim, Su Ssan;Lee, Seung Hak;Kim, Won;Choi, Chang-Min;Lee, Sei Won
    • Tuberculosis and Respiratory Diseases
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    • v.84 no.2
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    • pp.148-158
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    • 2021
  • Background: Radiotherapy is a common treatment option for lung or esophageal cancer, particularly when surgery is not feasible for patients with poor lung function. However, radiotherapy can affect pulmonary function and thereby induce pneumonitis or pneumonia, which can be fatal in patients with respiratory impairment. The purpose of this study is to evaluate if reductions in pulmonary function after radiotherapy can be minimized through simultaneous pulmonary rehabilitation (PR). Methods: In this matched case control study, we retrospectively analyzed patients who had undergone radiotherapy for thoracic malignant disease between January 2018 and June 2019. We analyzed results from pulmonary function tests and 6-minute walking tests (6MWT) conducted within the six months before and after radiotherapy treatment. Results: In total, results from 144 patients were analyzed, with 11 of the patients receiving PR and radiotherapy simultaneously. Of the 133 patients in the control group, 33 were matched with 11 patients in the PR group. Changes in forced expiratory volume in one second (FEV1) and FEV1/forced vital capacity were significantly different between the PR group and the matched control group (240 mL vs. -10 mL, p=0.017 and 5.5% vs. 1.0%, p=0.038, respectively). The median distance of 6MWT in the PR group also increased significantly, from 407.5 m to 493.0 m after radiotherapy (p=0.017). Conclusion: Simultaneous PR improved pulmonary function, particularly in measures of FEV1, and exercise capacity for patients with lung or esophageal cancer even after radiotherapy treatment. These findings may provide an important base of knowledge for further large population studies with long-term follow-up analysis in the identification of the PR's effects during thoracic radiotherapy.