• Title/Summary/Keyword: Radiation-induced Growth

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Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells

  • Cho, Won Kyung;Shin, Sung-Won;Kim, Shin-Yeong;Hong, Chang-Won;Choi, Changhoon;Park, Won;Noh, Jae Myoung
    • Radiation Oncology Journal
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    • v.34 no.3
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    • pp.223-229
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    • 2016
  • Purpose: This study is to investigate the effect of captopril when combined with irradiation. Materials and Methods: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha ($HIF-1{\alpha}$) of tumor was evaluated by immunohistochemical (IHC) staining. Results: The mean tumor volumes (${\pm}$standard error) at the 15th day after randomization were $1,382.0({\pm}201.2)mm^3$ (group 1), $559.9({\pm}67.8)mm^3$ (group 3), and $370.5({\pm}48.1)mm^3$ (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and $HIF-1{\alpha}$ positivity in tumor cells were decreased when treated with captopril. Conclusion: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.

Signal Transduction Factors on the Modulation of Radiosusceptibility in K562 Cells (K562 세포의 방사선 감수성 변화에 영향을 미치는 신호전달인자)

  • Yang Kwang Mo;Youn Seon-Min;Jeong Soo-Jin;Jang Ji-Yeon;Jo Wol-Soom;Do Chang-Ho;Yoo Y대-Jin;Shin Young-Cheol;Lee Hyung Sik;Hur Won Joo;Lim Young-Jin;Jeong Min-Ho
    • Radiation Oncology Journal
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    • v.21 no.3
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    • pp.227-237
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    • 2003
  • Purpose: The human chronic myelogenous leukemia cell line, K562, expresses the chimeric bcr-abl oncoprotein, whose deregulated protein tyrosine kinase activity antagonizes via DNA damaging agents. Previous experiments have shown that nanomolar concentrations of herbimycin A (HWA) coupled with X-irradiation have a synergistic effect in inducing apoptosis in the Ph-positive K562 leukemia cell line, but genistein, a PTK inhibitor, is non selective for the radiation-induced apoptosils on $p210^{bcr/abl}$ protected K562 cells. In these experiments, the cytoplasmic signal transduction pathways, the Induction on a number of transcription factors and the differential gene expression in this model were investigated. Materials and Methids: K562 cells in the exponential growth phase were used in this study. The cells were irradiated with 0.5-12 Gy, using a 6 Mev Linac (Clinac 1800, Varian, USA). Immediately after irradiation, the cells were treated with $0.25/muM$ of HMA and $25/muM$ of genistein, and the expressions and the activities of abl kinase, MAPK family, NF- kB, c-fos, c-myc, and thymidine kinase1 (TK1) were examined. The differential gene expressions induced by PTK inhibitors were also investigated. Results: The modulating effects of herbimycin A and genistein on the radiosensitivity of K562 cells were not related to the bcr-abl kinase activity. The signaling responses through the MAPK family of proteins, were not involved either in association with the radiation-induced apoptosis, which is accelerated by HMA, the expression of c-myc was increased. The combined treatment of genistein, with irradiation, enhanced NF- kB activity and the TK1 expression and activity. Conclusion: The effects of HMA and genistein on the radiosensitivity on the K562 cells were not related to the bcr-abl kinase activity in this study, another signaling pathway, besides the WAPK family responses to radiation to K562 cells, was found. Further evaluation using this model will provide valuable information for the optional radiosensitization or radioprotection.

Butyrate-induced differentiation of PC12 cells to chromaffin cells involves cell adhesion and induction of extracellular proteins and cell adhesion proteins

  • Heo, Jee-In;Oh, Soo-Jin;Kho, Yoon-Jung;Kim, Jeong-Hyeon;Kang, Hong-Joon;Park, Seong-Hoon;Kim, Hyun-Seok;Shin, Jong-Yeon;Lee, Sung-Young;Kim, Min-Ju;Min, Bon-Hong;Kim, Sung-Chan;Park, Jae-Bong;Kim, Jae-Bong;Lee, Jae-Yong
    • Animal cells and systems
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    • v.14 no.4
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    • pp.261-266
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    • 2010
  • PC12 cells were differentiated into the cells of chromaffin phenotype by butyrate treatment. Cells were aggregated and formed tight cell adhesion. To investigate the molecular change in this differentiation, we examined expression levels of cell adhesion proteins and extracellular proteins during butyrate induced-differentiation of PC12 cells. Integrin ${\beta}1$, integrin ${\alpha}7$, E cadherin, VCAM, collagen-I, fibronectin, desmoglein and connexin were increased during differentiation. The levels of clusterin and secreted clusterin were also increased. These increased levels of cell adhesion proteins and extracellular proteins appear to induce cell aggregation and tight cell adhesion. The levels of p21, p27 and p16 were increased probably because of differentiation-related growth arrest during differentiation. Prolonged incubation of butyrate up to 1 day was required for differentiation. Signal transduction pathways for this differentiatiom could not be identified since various inhibitors had no effect. The results showed that butyrateinduced differentiation of PC12 cells to chromaffin cells involves tight cell adhesion and induction of extracellular proteins and cell adhesion proteins.

Acceleration of Wound Healing on Scald Burn Skin Using Irradiation of TDP and Skin Spread of Myrrha

  • Cho Hyun Gug;Kim Keum-Suk;Lee Jong-wook
    • Biomedical Science Letters
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    • v.11 no.2
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    • pp.243-248
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    • 2005
  • The present study was conducted to determine whether skin spread of Myrrha and Tending Diancibo Pu (TDP) irradiation have a remarkable effect on the cell regeneration as well as wound healing following dermal scald burn injury. Burn injury was induced on dorsal surface $(TBSA\;15\~20\%)$ by scald burn in rats. Postburn concentration of serum protein was significantly decreased compared with sham-treated, double treatment with Myrrha and TDP was significantly increased the protein concentration compared with that of burn control. The content of keratinocyte growth factor (KGF) at 48 h is higher than that of at 24 h, and double treatment with Myrrha and TDP was the most effective to increase the production of KGF in all experimental groups. Morphologically, epithelial regeneration and dermal collagen synthesis by fibroblasts were accelerated in Myrrha and TDP treated group compared with bum control at same time postburn. At 48 h after burn, all dermal connective tissues are recovered to new collagen fibers in case of Myrrha and TDP double treated group. The data suggest that double treatment with skin spread of Myrrha and TDP radiation have a remarkable effect of to accelerate cell regeneration and wound healing in case of scald burn skin.

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Mutation of the invF Gene Encoding a Salmonella Pathogenicity Island 1 (SPI1) Activator Increases Expression of the SPI2 Gene, sseA (Salmonella Pathogenicity Island 1(SPI1)의 발현조절 유전자 invF의 변이가 SPI2 유전자(sseA)의 발현에 미치는 영향)

  • Han, Ah-Reum;Joe, Min-Ho;Kim, Dong-Ho;Baik, Sang-Ho;Lim, Sang-Yong
    • Microbiology and Biotechnology Letters
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    • v.40 no.1
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    • pp.70-75
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    • 2012
  • In Salmonella enterica, many genes encoded within Salmonella pathogenicity islands (SPI) 1 and 2 are required to cause a range of diseases in a variety of hosts. The SPI1-encoded regulator HilD activates both the SPI1 and 2 genes at different times during growth in Luria-Bertani (LB) media. In this study, the expression levels of hilD during growth in LB were investigated. The data suggest that hilD expression is induced in the early stationary phase and decreases in the late stationary phase, when sseA, an SPI2 gene, is maximally expressed. However, HilD could act as an activator of sseA expression in the late stationary phase despite being present at low levels. SseA expression was investigated in SPI1 regulator mutant strains, hilA, hilD and invF mutants. As expected, hilD mutation decreased sseA expression. However, we found that invF mutation caused a 1.5-fold increase in sseA expression in not only LB but also M9 minimal media, which is thought to resemble an intracellular environment. InvF overexpression restored sseA expression to wild-type levels in an invF mutant but did not cause an additional reduction in sseA expression. These results suggest that SPI1 controls SPI2 expression either positively or negatively.

A Literature Review of Management on Radiodermatitis (방사선 피부염 치료법에 대한 문헌고찰)

  • Kwon, Mi Hye;Yoon, Jee-Hyun;Kim, Eun Hye;Lee, Jee Young;Yoon, Seong Woo
    • Journal of Korean Traditional Oncology
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    • v.25 no.1
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    • pp.11-24
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    • 2020
  • Objective : Radiodermatitis is a common sequelae in 95% of patients receiving radiation therapy, which is important to be well managed as it can affect the patient's quality of life as well as the cancer treatment schedule. The aim of this study is to review and summarize the interventions available for the treatment of acute radiodermatitis, including traditional Korean medicine, and to propose treatment algorithms for clinicians. Methods : To collect studies about managements for radiodermatitis, domestic and foreign database were used such as Korean journal of traditional knowledge portal (KTKP), Korean studies information service system (KISS), national discovery or science leaders (NDSL), and oriental medicine advance searching integrated system (OASIS), Pubmed, Google scholar and Scopus. Results : Thirty-two studies were selected. There were nine studies on usual care and dressing, eleven studies on chemical agents, two studies on biological preparations, and ten studies on herbal medicines. Conclusion : Hygienic options and dressings have proved to be useful in the management of radiodermatitis. Chemical agents such as corticosteroid, statin, and topical antibiotic agent have proved to alleviate symptoms and severity, regenerate damaged skin, and prevent secondary infection. In biological preparations, EGF (epidermal growth factor) and GM-CSF (granulocyte-macrophage colony-stimulating factor) could be used to protect skin and prevent radiodermatitis. For herbal medicines, Calendula, catechin, β-sitosterol, and Jaungo (紫雲膏) may be effective for symptoms including pain, itching, and burning sensation induced by radiation therapy. Because of some research with conflicting results, further studies are needed to propose an algorithm for more optimal treatments.

In vitro Technique for Selection of Radiation Induced Mutants of Tall Fescue (방사선 처리에 의한 톨 페스큐 돌연변이 식물체 선발)

  • Lee, Ki-Won;Moon, Jin Young;Ji, Hee Chung;Choi, Gi Jun;Kim, Ki-Yong;Hwang, Tae Young;Lee, Sang-Hoon
    • Journal of Animal Environmental Science
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    • v.19 no.1
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    • pp.63-68
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    • 2013
  • In vitro culture and radiation techniques were used for obtaining mutants tin tall fescue. Endophyte free and friendly tall fescue cultivars Kentucky-31 and Jesup were used for induction of genetic variability through in-vitro mutagenesis. Mature seeds was used for callus induction on 6 mg/L 2,4-D. Actively growing and compact callus was treated with three different doses of gamma rays (10 Gy, 30 Gy and 50 Gy). Maximum proliferation and plantlets regeneration growth was observed in control and minimum at 10 Gy. Furthermore, the maximum number of tiller in the irradiated population was observed in 10 Gy. The treatments 30 Gy and 50 Gy exhibited negative impact on the tillering potential of the tall fescue plant. The object of this study was to develop protocols for mutation breeding in tall fescue through radiation techniques.

4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages

  • Lee, Jina;Choi, Jae-Won;Han, Hye Young;Kim, Woo Sik;Song, Ha-Yeon;Byun, Eui-Baek;Byun, Eui-Hong;Lee, Young-Ha;Yuk, Jae-Min
    • Parasites, Hosts and Diseases
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    • v.58 no.1
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    • pp.7-14
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    • 2020
  • Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human population worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effective drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4-HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs). Interestingly, treatment of BMDMs with 4-HBA significantly reduced the number of macrophages infected with T. gondii and the proliferation of T. gondii in infected cells. This effect was impaired by pretreating the macrophages with 3-methyladenine or wortmannin (selective autophagy inhibitors) or with sirtinol or EX527 (SIRT1 inhibitors). Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expression of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of T. gondii parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1-mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.

Application and Analysis of the Steady State Spectral Wave Model for Coastal Waters at Busan New Port Site (부산신항만수역에서 정상상태 스펙트럼 파랑모델의 적용 및 분석)

  • 이학승;이우철;황호동;양상용;이중우
    • Proceedings of the Korean Institute of Navigation and Port Research Conference
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    • 2003.05a
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    • pp.157-164
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    • 2003
  • Introduction of wave model, considered the effect of tide, wind and wave induced currents at the coastal waters of complex bathymetry, is a very important factor for most coastal engineering design and disaster protection problems. As the steady state spectral wave model could simulate depth induced wave shoaling and refraction, current induced refraction effect, steepness induced wave breaking, diffraction, wind wave growth, and wave-wave interaction that redistribute energy, this would support and compensate the gap in the real field of design where other wave models could not deal and cause wrong estimation. In this study, for that sense, we applied the spectral wave model t the large coastal waters near Gaduck Island where the Busan new port construction project is going on, for better understanding and analysis of wave transformation process. We also compared the simulation results with the calculated from the existing model. From such a trial of this study, we hope that broader and sager use of the spectral model in the area of port design and disaster prevention system come through in near future.

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Ginsenoside Rg3 increases gemcitabine sensitivity of pancreatic adenocarcinoma via reducing ZFP91 mediated TSPYL2 destabilization

  • Pan, Haixia;Yang, Linhan;Bai, Hansong;Luo, Jing;Deng, Ying
    • Journal of Ginseng Research
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    • v.46 no.5
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    • pp.636-645
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    • 2022
  • Background: Ginsenoside Rg3 and gemcitabine have mutual enhancing antitumor effects. However, the underlying mechanisms are not clear. This study explored the influence of ginsenoside Rg3 on Zinc finger protein 91 homolog (ZFP91) expression in pancreatic adenocarcinoma (PAAD) and their regulatory mechanisms on gemcitabine sensitivity. Methods: RNA-seq and survival data from The Cancer Genome Atlas (TCGA)-PAAD and Genotype-Tissue Expression (GTEx) were used for in-silicon analysis. PANC-1, BxPC-3, and PANC-1 gemcitabine-resistant (PANC-1/GR) cells were used for in vitro analysis. PANC-1 derived tumor xenograft nude mice model was used to assess the influence of ginsenoside Rg3 and ZFP91 on tumor growth in vivo. Results: Ginsenoside Rg3 reduced ZFP91 expression in PAAD cells in a dose-dependent manner. ZFP91 upregulation was associated with significantly shorter survival of patients with PAAD. ZFP91 overexpression induced gemcitabine resistance, which was partly conquered by ginsenoside Rg3 treatment. ZFP91 depletion sensitized PANC-1/GR cells to gemcitabine treatment. ZFP91 interacted with Testis-Specific Y-Encoded-Like Protein 2 (TSPYL2), induced its poly-ubiquitination, and promoted proteasomal degradation. Ginsenoside Rg3 treatment weakened ZFP91-induced TSPYL2 poly-ubiquitination and degradation. Enforced TSPYL2 expression increased gemcitabine sensitivity of PAAD cells and partly reversed induced gemcitabine resistance in PANC-1/GR cells. Conclusion: Ginsenoside Rg3 can increase gemcitabine sensitivity of pancreatic adenocarcinoma at least via reducing ZFP91 mediated TSPYL2 destabilization.