• Title/Summary/Keyword: Cell treatment

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Modulation of Cytotoxicity by Nitric Oxide Donors during Treatment of Glioma with Anticancer Drugs

  • Park, Jeong-Jae;Kang, Jong-Sool;Lee, Hyun-Sung;Lee, Jong-Soo;Lee, Young-Ha;Youm, Jin-Young
    • Journal of Korean Neurosurgical Society
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    • v.38 no.5
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    • pp.366-374
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    • 2005
  • Objective : Nitric oxide[NO] is implicated in a wide range of biological processes in tumors and is produced in glioma. To investigate the role of NO and its interaction with the tumoricidal effects of anticancer drugs, we study the antitumor activities of NO donors, with or without anticancer drugs, in human glioma cell lines. Methods : U87MG and U373MG cells were treated with the NO donors sodium nitroprusside[SNP] and S-nitroso-N-acetylpenicillamine[SNAP], alone or in combination with the anticancer drugs 1,3-bis[2-chloroethyl]-1-nitrosourea[BCNU] and cisplatin. Cell viability, cell proliferation, DNA fragmentation, nitrite level, and the expression of Bcl-2 and Bax were determined. Results : NO was markedly increased after treatment with SNP or SNAP; however, the addition of the anticancer drugs did not significantly affect NO production NO donors or anticancer drugs reduced glioma cell viability and, in combination, acted synergistically to further decrease cell viability in a dose- and time-dependent manner. Cell proliferation was inhibited and apoptosis were enhanced by combined treatment. Bax expression was increased by combined treatment, whereas Bcl-2 expression was reduced. The antitumor cytotoxicity of NO donors and anticancer drugs differed according to cell type. Conclusion : BCNU or cisplatin can inhibit cell viability and proliferation of glioma cells and can induce apoptosis. These effects are further enhanced by the addition of a NO donor which modulates the antitumor cytotoxicity of chemotherapy depending on cell type. Further biological, chemical, and toxicological studies of NO are required to clarify its mechanism of action in glioma.

Effects of Kimchi Extracts on Interleukin-2 Production and Natural Killer Cell Activity in Mice

  • Kim, Kwang-Hyuk;Kim, So-Hee;Rhee, Sook-Hee;Park, Kun-Young
    • Preventive Nutrition and Food Science
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    • v.3 no.3
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    • pp.282-286
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    • 1998
  • To determine the immune effect of kimchi extracts in mice, 0.5mg/day of the extracts from kimchis, which were prepared with conventionally (general kimchi)and organically(organic kimchi) cultivated ingredients, were treated orally to male BALB/c mice. Following 1, 3 and 5 weeks of treatment , the Interleukin-2(IL-2) production in the presence (con-A-stimulated )or the absence(spontaneous)of con A 95 $\mu\textrm{g}$/ml) and the natural killer cell (NK) activity of the splenocytes were measured. The IL-2 production in most of treatments with methanol extract from general kimchi were significantly higher than those of control(p<0.05).And at the 3 weeks of treatment, the spontaneous or con A-stimulated IL-2 productions from splenocytes of mice treated with it increased more than those of control group, by 2.8 and 2.2 times, respectively. However, the longer the treatment with methanol extracts from organic kimchi showed the higher the enhancing effect on the IL-2 production. The spontaneous or con A-stimulatdIL-2 productions form splenocytes of mice treated with dicholoromethyane fraction from general kimchi also increased at 5 weeks of treatment compared to those of control group, by 2.7 and 2.5 times, respectively. The natural killer cell activity of splenocytes from mice treated with methano lextracts from general kimchi for 1 ~5 weeks significantly higher than that of control goup (p<0.01). The effect of methano extracts from general kimchi was the highest at 3 weeks of treatment, as same as in the IL-2 production. The enhancing effect of methano extracts from organic kimchi on the NK cell activity was the highest at 5 weeks of treatment . The NK cell activity of splenocytes from mice treated with dichloromethane fraction from general kimchi for 5 weeks was significantly higher than those in control and 3 weeks of treatment. These results showed that the effects of kimchi extracts on the IL-2 production and the NK cell activity in mice were profound in long term of treatment (3 and 5 weeks than 1 week) . We suggest that kimchi extracts might have an immune effect in part due to its enhancing action on the IL-2 production and the NK cell activity.

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Effects of Leptin on Osteoclast Generation and Activity

  • Ko, Seon-Yle;Cho, Sang-Rae;Kim, Se-Won;Kim, Jung-Keun
    • International Journal of Oral Biology
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    • v.30 no.2
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    • pp.47-57
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    • 2005
  • Leptin, the product of the obese gene, is a circulating hormone secreted primarily from adipocytes. Several results suggest that leptin is important mediators of bone metabolism. The present study was undertaken to determine the effects of leptin on anti-osteoclastogenesis using murine precursors cultured on Ca-P coated plates and on the production of osteoprotegerin (OPG) in osteoblastic cells. Additionally, this study examined the possible involvement of prostaglandin $E_2\;(PGE_2)$/protein kinase C (PKC)-mediated signals on the effect of leptin on anti-osteoclastogenesis to various culture systems of osteoclast precursors. Osteoclast generation was determined by counting tartrate-resistant acid phosphatase positive [TRAP (+)] multinucleated cells (MNCs). Osteoclastic activity was determined by measuring area of resorption pits formed by osteoclasts on Ca-P coated plate. The number of 1,25-dihydroxycholecalciferol $(1,25[OH]_2D_3)$- or $PGE_2$-induced TRAP (+) MNCs in the mouse bone marrow cell culture decreased significantly after treatment with leptin. The number of receptor activator of NF-kB ligand (RANKL)-induced TRAP (+) MNCs in M-CSF dependent bone marrow macrophage (MDBM) cell or RAW264.7 cell culture decreased significantly with leptin treatment. Indomethacin inhibited osteoclast generation induced by $1,25[OH]_2D_3$ and dexamethasone, however, no significant differences were found in the leptin treated group when compared to the corresponding indomethacin group. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, inhibited osteoclast generation induced by $1,25[OH]_2D_3$. The number of TRAP (+) MNCs decreased significantly with treatment by PMA at concentrations of 0.01 and $0.1{\mu}M$ in culture. Leptin inhibited PMA-mediated osteoclast generation. Isoquinoline-5-sulfonic 2-methyl-1-piperazide dihydrochloride (H7) had no effect on osteoclast generation induced by $1,25[OH]_2D_3$. Cell culture treatment with leptin resulted in no significant differences in osteoclast generation compared to the corresponding H7 group. Indomethacin showed no significant effect on TRAP (+) MNCs formation from the RAW264.7 cell line. PMA inhibited TRAP (+) MNCs formation induced by RANKL in the RAW264.7 cell culture. H7 had no effect on osteoclast generation from the RAW264.7 cell line. There was no difference compared with the corresponding control group after treatment with leptin. $1,25[OH]_2D_3$- or $PGE_2$-induced osteoclastic activity decreased significantly with leptin treatment at a concentration of 100 ng/ml in mouse bone marrow cell culture. Indomethacin, PMA, and H7 significantly inhibited osteoclastic activity induced by $1,25[OH]_2D_3$ in mouse bone marrow cell culture. No significant differences were found between the leptin treated group and the corresponding control group. The secretion of OPG, a substance known to inhibit osteoclast formation, was detected from the osteoblasts. Treatment by leptin resulted in significant increases in OPG secretion by osteoblastic cells. Taken these results, leptin may be an important regulatory cytokines within the bone marrow microenvironment.

Therapeutic Effects of Safflower Seed Extract and Chitosan on Hard Tissue Regeneration (홍화자 추출물과 키토산 병용처리에 의한 경조직 재생촉진 효과)

  • 정세영;박준봉;권영혁;김성진;박건구
    • Biomolecules & Therapeutics
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    • v.9 no.4
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    • pp.244-248
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    • 2001
  • This study was performed to investigate therapeutic effects of Carthami Semen, Paeoniae Raidx extracts and chitosan on the growth and differentiation of human periodontal ligament cell. We found that co-treatment of methanol extracts of Carthami Semen and chitosan significantly increased the growth of human periodontal ligament cell. However, the sigle treatment groups of the extracts showed only 20-30% of the growth increase. Alkaline phosphase activity, one of differentiation markers, was increased approximately 1.5- fold by co-treatment of methanol extract of Carthami Semen and chitosan and calcified nodule formation was also increased at the similar levels as the alkaline phosphatase. But the single treatment groups showed only 20-30% increases. These results suggest that Carthami Semen and chitosan co-treatment can be used efficiently for periodontium regeneration.

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MODULATION OF IRRADIATION-INDUCED CELL DEATH BY INSULIN-LIKE GROWTH FACTOR-II IN MC3T3 OSTEOBLASTS (Insulin-like growth factor-II가 방사선에 의한 MC3T3 조골세포의 세포사멸에 미치는 영향)

  • Park, Kyeong-Lok
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.6
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    • pp.617-624
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    • 2007
  • Insulin-like growth factor(IGF) is the most abundant growth factor in bone matrix. Recent studies have shown that it can sensitize apoptotic cell death of osteoblasts. Thus, this study investigated whether IGF-II aggravates irradiation-induced cell death of osteoblasts. Cultured MC3T3 osteoblasts were irradiated and IGF-II was added at the concentration of 50 ng/ml immediately after the irradiation. Cell viability was measured by MTT assay. Changes in cell death and cell cycle were analyzed by flow cytometry. The expression of proapoptotic gene bax and antiapoptotic gene bcl-2 was quantified by real time RT-PCR and Western blot. A dose of 30 Gy caused G2/M arrest and increased cell death through both necrosis and apoptosis, while irradiation from 4 to 10 Gy little affected cell cycle and death. IGF-II treatment reduced cell viability without stimulating cell proliferation and changing cell cycle. Combined treatment of IGF-II with irradiation decreased cell viability and proliferation and increased cell death along with G2/M arrest. These effects were not different from those of irradiation only. At transcriptional and protein levels, IGF-II treatment did not affect bax and bcl-2 expression, whereas irradiation increased the expression ofbax without changes in bcl-2. IGF-II in combination with irradiation showed similar findings. These results suggest that IGF-II could modulate apoptotic cell death through mechanisms other than an imbalance between bax and bcl-2 gene expression, although its effect was overridden by irradiation.

Seedling Quality, and Early Growth and Fruit Productivity after Transplanting of Squash as Affected by Plug Cell Size and Seedling Raising Period (플러그 셀 크기와 육묘일수에 따른 애호박의 묘 소질, 정식 후 초기 생육 및 과실 생산성)

  • Kim, Yeong Sook;Park, Yoo Gyeong;Jeong, Byoung Ryong
    • Journal of Bio-Environment Control
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    • v.28 no.3
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    • pp.185-196
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    • 2019
  • Abstract. This research was conducted to figure out the optimal size of the plug cell and seedling raising period in 'Nongwoo' and 'Nonghyeop' cultivars. In the first experiment on effect of plug cell size on growth of squash, seedlings were transplanted into hydroponic cultivation beds at different growing stages: Those in 32-cell trays with 3-4 true leaves at 25 days after sowing, those in 50-cell trays with 2 true leaves at 15 days after sowing, those in 105-cell trays just before a true leaf development, and those in 162-cell trays with only cotyledons at 8 days after sowing. In the second experiment on effect of seedling raising period on growth of squash, it was conducted to have different sowing dates. But the same transplanting date, based on the results of Experiment 1, and compared the differences in growth and fruit productivity as affected by plug cell size in the same way with experiment 1 including the cultivars and environmental conditions. After setting the transplanting date in advance, the number of days for sowing were calculated back for each treatment. In the first experiment, plant height was the greatest in 105-cell trays followed by 162, 50 and 32-cell trays in both cultivars. The best fruit quality was found in different treatments depending on the cultivars, although it was the lowest in 32-cell trays in both cultivars. The fruit quality was not significantly different among those from cell sizes. Therefore, when raising seedlings in 105-cell trays, the period of raising seedlings can be shortened as compared with the conventional 32-cell trays, and this change could reduce the workforce required for growing and transplanting seedlings. In the second experiment, after transplanting, shoot height and leaf width in the first measurement in both cultivars were greater in the 32-cell treatment. However, the last measurement after four weeks showed no significant difference in plant height, but significantly greatest leaf width in the smallest cell treatment, even as compared with that in 32-cell treatment. In case of 'Nongwoo', length and weight of the first harvested fruit showed the highest values in the treatment of 105-cell trays. In case of 'Nonghyeop' the 162-cell treatment along with the 105-cell treatment showed greatest length and weight of the first fruits. From these results, zucchini plug seedlings can be raised in plug trays with reduced cell sizes than the conventional 32-cell trays with improved fruit productivity.

Synergistic Effect of Ethaselen and Selenite Treatment against A549 Human Non-small Cell Lung Cancer Cells

  • Xu, Wei;Ma, Wei-Wei;Zeng, Hui-Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7129-7135
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    • 2014
  • Background: In this study, we aimed to evaluate the growth inhibitory effect of the combination of ethaselen (BBSKE) and low fixed dose of selenite against A549 human non-small cell lung cancer cells in vitro. Materials and Methods: Growth inhibitory effects against A549 cells were determined by SRB assay. Combination index (CI) values were calculated based on Chou-Talalay median-effect analyses. Dose reduction index (DRI) values were applied to calculate dose reduction of selenite. Contents of free thiols and GSH were determined by DTNB assay and intracellular ROS levels by DCFH-DA fluorescence labeling. Results: Compared with BBSKE or selenite single treatment, the combined application of ethaselen and a low fixed dose of selenite shortened the onset time of sodium selenite, reduced $IC_{50}$ values, and increased the maximum inhibition rates, suggesting a possible molecular mechanism of the synergism. Obvious synergistic effects were observed after different times of combination treatment, especially after 24 h. Compared with selenite single treatment, dosage of selenite could be remarkably reduced in combination therapy to gain the same inhibitory effect on cell proliferation. Compared with BBSKE single treatment, the content of free thiols and GSH were significantly reduced and ROS levels greatly elevated in the combination group. For the combination treatment, cell viability increased as greater concentrations of GSH were added. Conclusions: All these results indicate that the combination treatment of BBSKE and selenite showed synergism to inhibit A549 cell proliferation in vitro, and also reduced the selenite dosage to mitigate its toxicity which is very meaningful for combination chemotherapy of lung cancer. The synergism was probably caused by the accelerated exhaustion of intracellular reductive substances, such as free thiols and GSH, which ultimately leads to enhanced oxidative stress and apoptosis.

Effects of Bisphosphonates on Glucose Transport in a Conditionally Immortalized Rat Retinal Capillary Endothelial Cell Line (TR-iBRB Cells)

  • Lee, Na-Young;Park, Hyun-Joo;Kang, Young-Sook
    • Biomolecules & Therapeutics
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    • v.24 no.1
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    • pp.94-98
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    • 2016
  • The objective of the present study was to elucidate the effect of bisphosphonates, anti-osteoporosis agents, on glucose uptake in retinal capillary endothelial cells under normal and high glucose conditions. The change of glucose uptake by pre-treatment of bisphosphonates at the inner blood-retinal barrier (iBRB) was determined by measuring cellular uptake of $[^3H]3$-O-methyl glucose (3-OMG) using a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB cells) under normal and high glucose conditions. $[^3H]3$-OMG uptake was inhibited by simultaneous treatment of unlabeled D-glucose and 3-OMG as well as glucose transport inhibitor, cytochalasin B. On the other hand, simultaneous treatment of alendronate or pamidronate had no significant inhibitory effect on $[^3H]3$-OMG uptake by TR-iBRB cells. Under high glucose condition of TR-iBRB cells, $[^3H]3$-OMG uptake was increased at 48 h. However, $[^3H]3$-OMG uptake was decreased significantly by pre-treatment of alendronate or pamidronate compared with the values for normal and high glucose conditions. Moreover, geranylgeraniol (GGOH), a mevalonate pathway intermediate, increased the uptake of $[^3H]3$-OMG reduced by bisphosphonates pre-treatment. But, pre-treatment of histamine did not show significant inhibition of $[^3H]3$-OMG uptake. The glucose uptake may be down regulated by inhibiting the mevalonate pathway with pre-treatment of bisphosphonates in TR-iBRB cells at high glucose condition.

Effects of Liriope muscari Water Extracts on the Cell Death and Inflammatory Cytokine Expression of Poly I:C-treated Lung Carcinoma Cells (맥문동 열수 추출물이 Poly I:C를 처리한 폐암세포주의 사멸 및 염증성 사이토카인 발현에 미치는 영향)

  • Kang, Dayeon;Cho, Namjoon;Renchinkhand, Gereltuya;Lee, Bo-Hee;Kim, Eun-Mi;Nam, Myoung Soo;Kim, Keekwang
    • The Korea Journal of Herbology
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    • v.36 no.1
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    • pp.97-102
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    • 2021
  • Objectives : Virus infection through the respiratory tract causes various inflammatory diseases such as pneumonia, cystic fibrosis, and obstructive pulmonary disease, causing enormous social damage. Therefore, it is very important to develop a treatment and prevention of infectious diseases. In this study, we investigated the effect of water extracts of Liriope muscari (WELM), known to improve lung function, on the inflammatory response of lung carcinoma cell line A549 cells induced by the viral double stranded RNA mimetic Polyinosinic:polycytidylic acid (Poly I:C). Methods : The cell viability by WELM treatment was analyzed using MTS assay in A549 cells. After inducing an inflammatory response to WELM-treated A549 cells with Poly I:C, the degree of apoptosis was confirmed through bright field microscopy. Interferon beta (IFN-β) mRNA expression level in A549 cells was analyzed by quantitative reverse transcription PCR (qRT-PCR). Results : WELM treatment has no significant effect on cell viability of A549 cells. We confirmed that pre-treatment of WELM effectively reduces the Poly I:C-induced apoptotic cell death in A549 cells. In addition, it was confirmed that the mRNA expression level of IFN-β, a pro-inflammatory cytokine increased by Poly I:C treatment, was significantly suppressed by WELM treatment in A549 cells. Conclusions : These results provide the evidence that WELM is effective at inhibiting inflammation on respiratory viral infections and suggest that Liriope muscari might be a valuable natural substance in the prevention and treatment of infectious diseases.

Advancements in the treatment of pediatric acute leukemia and brain tumor - continuous efforts for 100% cure

  • Ju, Hee Young;Hong, Che Ry;Shin, Hee Young
    • Clinical and Experimental Pediatrics
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    • v.57 no.10
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    • pp.434-439
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    • 2014
  • Treatment outcomes of pediatric cancers have improved greatly with the development of improved treatment protocols, new drugs, and better supportive measures, resulting in overall survival rates greater than 70%. Survival rates are highest in acute lymphoblastic leukemia, reaching more than 90%, owing to risk-based treatment through multicenter clinical trials and protocols developed to prevent central nervous system relapse and testicular relapse in boys. New drugs including clofarabine and nelarabine are currently being evaluated in clinical trials, and other targeted agents are continuously being developed. Chimeric antigen receptor-modified T cells are now attracting interest for the treatment of recurrent or refractory disease. Stem cell transplantation is still the most effective treatment for pediatric acute myeloid leukemia (AML). However, in order to reduce treatment-related death after stem cell transplantation, there is need for improved treatments. New drugs and targeted agents are also needed for improved outcome of AML. Surgery and radiation therapy have been the mainstay for brain tumor treatment. However, chemotherapy is becoming more important for patients who are not eligible for radiotherapy owing to age. Stem cell transplant as a means of high dose chemotherapy and stem cell rescue is a new treatment modality and is often repeated for improved survival. Drugs such as temozolomide are new chemotherapeutic options. In order to achieve 100% cure in children with pediatric cancer, every possible treatment modality and effort should be considered.