• Title/Summary/Keyword: nuclear fragmentation

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Synergistic Effects of 5-Fluorouracil (FU) and Curcumin on Human Cervical Cancer Cells (5-fluorouracil과 curcumin의 복합투여에 의한 자궁암세포의 성장억제와 p53유전자 발현의 상승 효과)

  • Ahn, Seong-Ho;Kim, Dong-Heui;Kang, Jung-Hoon;Lee, Myeong-Seon
    • Applied Microscopy
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    • v.40 no.4
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    • pp.229-235
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    • 2010
  • Cervical cancer is associated with low antioxidant status. It has a high prevalence especially amongst woman in Asia and is a leading cause of cancer death. Cancer chemotherapy in vivo improved in cases with high p53 expression in the tumor tissue. The restoration of p53 levels could be a potential strategy to increase chemoresponsiveness. Under circumstances where damage is extensive, p53 plays a direct role in trigering apoptosis. To investigate the effect of curcumin (CMN) as an antioxidant agent on anticancer agent 5-fluorouracil (5FU) induced apoptosis and p53 expression, HPV-18 positive HeLa cells were treated with noncytotoxic amounts of antioxidant. Curcumin induced apoptosis in cervical cancer cells. Morphological hallmarks of apoptosis such as nuclear fragmentation and internucleosomal fragmentation of DNA were observed. CMN caused upregulation of p53 expression, evident from Western blotting data and also increased the susceptibility/apoptosis induced by 5FU. These results show that increasing drug sensitivity of cervical cancer cells by upregulation of p53 using CMN is novel approach and could have a possible therapeutic potential in cervical cancer.

Pseudomonas aeruginosa Exotoxin A Induces Apoptosis in Chemoresistant YD-9 Human Oral Squamous Carcinoma Cell Line Via Accumulation of p53 and Activation of Caspases (항암제에 저항성을 가지는 YD-9 human oral squamous carcinoma cell line에서 Pseudomonas aeruginosa exotoxin A의 p53 단백질 누적과 caspase를 활성화 경로를 통해 유도된 세포자멸사)

  • Kim, Gyoo-Cheon;Gil, Young-Gi
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1047-1054
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    • 2009
  • Oral squamous carcinoma (OSC) cells present resistance to chemotherapeutic agents-mediated apoptosis in the late stages of malignancy. Advances in the understanding of bacterial toxins have produced new strategies for the treatment of cancers. It was demonstrated here that Pseudomonas aeruginosa exotoxin A (PEA) significantly decreased the viability of chemoresistant YD-9 cells in the apoptosis mechanism. Apoptotic manifestations were evident through changes in nuclear morphology and generation of DNA fragmentation. PEA treatment induced caspase-3, -6 and -9 cleavage, and activation. These events preceded proteolysis of the caspase substrates poly (ADP-ribose) polymerase (PARP), DNA fragmentation factor 45 (DFF45), and lamin A in YD-9 cells. The reduction of mitochondrial membrane potential, release of cytochrome c and SmacjDlABLO from mitochondria to cytosol, andtranslocation of AlF into nucleus were shown. While p53, p21 and $14-3-3{\gamma}$ were upregulated, cyclin Band cdc2 were downregulated by PEA treatment. Taken together, PEA induces apoptosis in chemoresistant YD-9 cells via activation of caspases, mitochondrial events and regulation of cell cycle genes.

Growth Inhibition and Apoptosis Induction of Sulindac on Human Lung Cancer Cells (비소세포 폐암 세포주에서 Sulindac의 성장억제와 세포고사 유도)

  • Kim, Hak Ryul;Yang, Sei Hoon;Jeong, Eun Taik
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.5
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    • pp.514-522
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    • 2004
  • Background : Non-steroidal anti-inflammatory drugs (NSAID) are useful in chemoprevention of colorectal cancers. Continuous NSAID administation causes 40% to 50% reduction in relative risk for colorectal cancer. Sulindac possesses an antiproliferative effect and induces apoptosis and tumor regression on colon cancer and other types of cancers. We intended to analyze the effects of sulindac in three non-small cell lung cancer cell lines. Materials and Methods : The human lung cancer cell lines, A549, NCI-H157 and NCI-H460 were used for this study. Viability was tested by MTT assay, and cell death rate was measured by lactate dehydrogenase(LDH) release. Apoptosis was estimated by flow cytometric analysis and nuclear staining. Results: Sulindac was able to decrease the viability of non-small cell lung cancer cells in a dose- and time- dependent manner. In a parallel effect of sulindac on cell death rate, LDH release was increased in sulindac-treated lung cancer cells. Sulindac significantly increased apoptosis characterized by an increase of $sub-G_0/G_1$ fraction and morphological change of nuclei. The rate of apoptotic cells after sulindac treatment in lung cancer cells increased in a time- and dose- dependent manner in flow cytometric analysis. Apoptotic cells were defined as nuclear shrinkage, chromatin condensation and nuclear fragmentation of cells. Conclusion : Sulindac decreases viability and induces the apoptosis of lung cancer cells. Further studies will be needed to elucidate the potential mechanism of sulindac-induced apoptosis in lung cancer cells.

Histochemical and Fine Structural Visualization of the Epithelial Apoptosis in the Anuran Tadpole during the Tail Regression Stages (무미양서류 꼬리 퇴화과정중 피부 상피조직의 세포사에 관한 조직화학적 및 미세구조적 연구)

  • Lee, Hye-Won;Moon, Myung-Jin
    • Applied Microscopy
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    • v.39 no.2
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    • pp.107-115
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    • 2009
  • The programed cell death of the cutaneous epithelial tissue during tail regression stages in anuran tadpoles of the blackspotted frog, Rana nigromaculata were visualized by the histochemical and transmission electron microscopic techniques. Metamorphotic changes in the tail regression during the period of the Shumway stage number 31 to 33 are characterized by the disappearance of mucous layer and formation of compound epithelium through cutaneous thickening. Following the TUNEL (terminal deoxynucleotidyl transferase-mediated biotinylated d-uridine triphosphate nick end labeling) staining technique, the apoptotic cells were detected at the distal region of the tail skin initially, but they can be seen at the proximal region according to their following development. It has been also revealed that the number of the TUNEL-positive cells gradually increased from apical to basal direction of the epithelial layers during the tail regressing stages. Following the TEM observation, the early apoptotic cells shown in the epithelium demonstrated condensation and margination of the chromatin material at the nuclear periphery. Another epithelial apoptotic cells were shown nuclear fragmentation, membrane blebbing and cytoplasmic condensation. Following the process of the apoptotic degradation, well preserved organelles and nuclear fragments can be identified in the cytoplasm of lysosome-rich cells, however they soon reduced to lysosomal residual bodies through the progressive degradation.

Protective Effects of Bojungmyunyuk-dan in Cisplatin Treated Brain Cell Death (Cisplatin에 의한 뇌세포사멸에서 보중면역단의 방어효과)

  • Yoo Kyung Tae;Moon Seok Jae;Won Jin Hee;Kim Dong Woung;Lee Jong Deok;Won Kyoung Sook;Moon Goo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.2
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    • pp.394-402
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    • 2003
  • This study was designed to investigate the protective effect of Bojungmyunyuk-dan(BJMY-Dan) on the cisplatin-induced cytotoxicity of primary rat astrocytes. BJMY-Dan is an oriental herbal prescription for its ability to recover protective effects against anti-cancer chemotherapies. After astrocytes were treated cisplatin, MTT assay was performed for cell viability test. To explore the mechanism of cytotoxicity, I used the several measures of apoptosis to determine whether this processes was involved in cisplatin-induced cell damage in astrocytes. Also, astrocytes were treated with BJMY-Dan and then, followed by the addition of cisplatin. Cisplatin decreased the viability of astrocytes in a dose and time-dependent manner. BJMY-Dan increased the viability of astrocytes treated cisplatin. Astrocytes treated cisplatin were revealed as apoptosis characterized by nuclear staining and flow cytometry. BJMY-Dan protected astrocytes from cisplatin-induced nuclear fragmentation and chromatin condensation. Also, caspase-3 and caspase-9 proteases were activated in astrocytes by cisplatin. BJMY-Dan inhibited the activation of caspase proteases in cisplatin-treated astrocytes. Cleavage of [poly(ADP-ribose) polymerase](PARP) was occurred at 12hr after treatment of cisplatin in astrocytes. BJMY-Dan recovered the cleavage of PARP in cisplatin-treated astrocytes. Also, BJMY-Dan inhibited the activation of pro-apoptotic factor, Bak by cisplatin. Lastly, astrocytes stained with JC-1 and Rhodamine 123 were photographed by fluorescence microscope to visualize changes of mitochondrial membrane permeability transition(MPT) during treatment with cisplatin for 24hr. BJMY-Dan recovered the change of MPT by cisplatin in astrocytes. According to above results, BJMY-Dan may protect astrocytes from cytotoxicity induced by chemotherapeutic agents, including cisplatin.

The Effect of PET Scan Time on the Off-Line PET Image Quality in Proton Therapy (양성자 치료에서 영상 획득 시간에 따른 Off Line PET의 효율성 검증)

  • Hong, Gun-Chul;Jang, Joon-Yung;Park, Se-Joon;Cha, Eun-Sun;Lee, Hyuk
    • The Korean Journal of Nuclear Medicine Technology
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    • v.21 no.2
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    • pp.74-79
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    • 2017
  • Purpose Proton therapy can deliver an optimal dose to tumor while reducing unnecessary dose to normal tissue as compared the conventional photon therapy. As proton beams are irradiated into tissue, various positron emitters are produced via nuclear fragmentation reactions. These positron emitters could be used for the dose verification by using PET. However, the short half-life of the radioisotopes makes it hard to obtain the enough amounts of events. The aim of this study is to investigate the effect of off-line PET imaging scan time on the PET image quality. Materials and Methods The various diameters of spheres (D=37, 28, 22 mm) filled with distilled water were inserted in a 2001 IEC body phantom. Then proton beams (100 MU) were irradiated into the center of the each sphere using the wobbling technique with the gantry angle of $0^{\circ}$. The modulation widths of the spread out bragg peak were 16.4, 14.7 and 9.3 cm for the spheres of 37, 28 and 22 mm in diameters respectively. After 5 min of the proton irradiation, the PET images of the IEC body phantom were obtained for 50 min. The PET images with different time courses (0-10 min, 11-20 min, 21-30 min, 31-40 min and 41-50 min) were obtained by dividing the frame with a duration of 10 min. In order to evaluate the off-line PET image quality with the different time courses, the contrast-to-noise ratio (CNR) of the PET image calculated for each sphere. Results The CNRs of the sphere (D=37 mm) were 0.43, 0.42, 0.40, 0.31 and 0.21 for the time courses of 0-10 min, 11-20 min, 21-30 min, 31-40 min and 41-50 min respectively. The CNRs of the sphere (D=28 mm) were 0.36, 0.32, 0.27, 0.19 and 0.09 for the time courses of 0-10 min, 11-20 min, 21-30 min, 31-40 min and 41-50 min respectively. The CNR of 37 mm sphere was decreased rapidly after 30 min of the proton irradiation. In case of the spheres of 28 mm and 22 mm, the CNR was decreased drastically after 20 min of the irradiation. Conclusion The off-line PET imaging time is an important factor for the monitoring of the proton therapy. In case of the lesion diameter of 22 mm, the off-line PET image should be obtained within 25 min after the proton irradiation. When it comes to small size of tumor, the long PET imaging time will be beneficial for the proton therapy treatment monitoring.

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Magnolol Attenuates Neuronal Cell Death Induced by Kynurenine Metabolite (키누레닌 대사산물에 의한 신경세포 손상에 대한 Magnolol의 보호효과에 대한 연구)

  • Lee, Chang-Uk;Lee, Hyun-Jung;Kim, Do-Hee;Jang, Yeong-Mi;Lee, Sang-Hyung;Jeong, Yoonh-Wa;Kim, Dae-Jin;Chung, Yoon-Hee;Kim, Kyung-Yong;Kim, Sung-Su;Lee, Won-Bok
    • Korean Journal of Medicinal Crop Science
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    • v.17 no.2
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    • pp.145-150
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    • 2009
  • This study investigated the protective roles and mechanism of magnolol, from the stem bark of Magnolia officinalis against potential neurotoxin 3-hydroxykynurenine (3-HK)-induced neuronal cell death. For the evaluation of protective role of magnolol, we examined cell viability, apoptotic nuclei, change of mitochondrial membrane potential and caspase activity in human neuroblastoma SH-SY5Y cells. It was found that 3-HK induces neuronal cell death in the human neuroblastoma SH-SY5Y cell line. The reduced cell viability produced characteristic features such as cell shrinkages, plasma membrane blebbing, chromatin condensation, and nuclear fragmentation. The cells treated with 3-HK showed an increase in the concentration of reactive oxygen species (ROS) as well as in caspase activity. In addition, both are involved in the 3-HK-induced apoptosis. Magnolol attenuated the cell viability reduction by 3-HK in both a dose- and time-dependent manner. Optical microscopy showed that magnolol inhibited the cell morphological features in the 3-HK-treated cells. Furthermore, the increase in the ROS concentration and the caspase activities by 3-HK were also attenuated by magnolol. These results showed that magnolol has a protective effect on the 3-HK induced cell death by inhibiting ROS production and caspase activity.

Multiple Outbursts of a Short-Periodic Comet 15P/Finlay

  • Ishiguro, Masateru;Kuroda, Daisuke;Kim, Yoonyoung;Kwon, Yuna;Hanayama, Hidekazu;Miyaji, Takeshi;Honda, Satoshi;Takahashi, Jun;Watanabe, Jun-Ichi
    • The Bulletin of The Korean Astronomical Society
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    • v.40 no.1
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    • pp.61.2-61.2
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    • 2015
  • 15P/Finlay is one of the Jupiter-Family Comets that has long been known since the late 19 century. The comet maintains the perihelion around 1.0 AU over a century, without showing any prominent activities (i.e. fragmentation or eruption) since the discovery. According to reports in unpublished observations, the comet exhibited an outburst in the middle of 2014 December. We conducted a imaging observation of 15P/Finlay just after the report, from 2014 December 23 to 2015 February 18 using three telescopes (the Okayama Astrophysical Observatory 50-cm telescope, the Ishigakijima Astronomical Observatory 105-cm telescope, and the Nishi-Harima Astronomical Observatory 2-m telescope), which constitute a portion of the OISTER (an inter-university observation network in the optical and infrared wavelengths). As a result of the frequent observations, we witnesses the second outburst around UT 2015 January 16. Such cometary outbursts draw the attention to researchers on ground that they could offer insight into the internal structure of comets, following a historical outburst occurred at 17P/Holmes on 2007 October 23. Although cometary outbursts have been often reported mostly in unpublished observations or unreviewed reports, it should be emphasized that there are not a sufficient number of astrophysical research which characterizes the physical properties by observing the aftermaths. This presentation provides a new observational result of 15P/Finlay outburst. Based on the morphological development of the dust cloud as well as the near-nuclear magnitude, we will derive the kinetic energy of the outburst. Finally we plan to compare the results of 15P/Finlay with those of analogical events at 17P/Holmes and P/2010 V1 (Ikeya-Murakami).

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Apoptotic Effect of Co-treatment with Curcumin and Cisplatin on SCC25 Human Tongue Squamous Cell Carcinoma Cell Line

  • Sohn, Hyeon-Jin;Kim, In-Ryoung;Kim, Yong-Ho;Kim, Gyoo-Cheon;Kwak, Hyun-Ho;Park, Bong-Soo
    • International Journal of Oral Biology
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    • v.39 no.3
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    • pp.159-167
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    • 2014
  • Curcumin is a widely used flavoring agent in food, and it has been reported to inhibit cell growth, to induce apoptosis, and to have antitumor activity in many cancers. Cisplatin is one of the most potent known anticancer agents and shows significant clinical activity against a variety of solid tumors. This study was undertaken to investigate the synergistic apoptotic effects of co-treatment with curcumin and cisplatin on human tongue SCC25 cells. To investigate whether the co-treatment efficiently reduced the viability of the SCC25 cells compared with the two treatments separately, an MTT assay was conducted. The induction and the augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining, and an analysis of DNA hypoploidy. Western blot, MMP and immunofluorescence tests were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following the co-treatment. In this study, following the co-treatment with curcumin and cisplatin, the SCC25 cells showed several forms of apoptotic manifestation, such as nuclear condensation, DNA fragmentation, reduction of MMP, increased levels of Bax, decreased levels of Bcl-2, and decreased DNA content. In addition, they showed a release of cytochrome c into the cytosol, translocation of AIF and DFF40 (CAD) to the nuclei, and activation of caspase-7, caspase-3, PARP, and DFF45 (ICAD). In contrast, separate treatments of $5{\mu}M$ of curcumin or $4{\mu}g/ml$ of cisplatin, for 24 hours, did not induce apoptosis. Therefore, our data suggest that combination therapy with curcumin and cisplatin could be considered as a novel therapeutic strategy for human oral squamous cell carcinoma.

Histopathological observation of the crucian carp Carassius auratus with infected leech Limnotrachelobdella sinensis by scanning electron microscope (주사전자현미경을 이용한 거머리, Limnotrachelobdella sinensis 감염 붕어, Carassius auratus의 조직병리학적 관찰)

  • Park, Jung-Jun;Byoun, Ju-Young;Kim, Jung-Ho;Choi, Hye-Sung;Park, Myoung-Ae;Kim, Seok-Ryel
    • Journal of fish pathology
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    • v.24 no.3
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    • pp.205-211
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    • 2011
  • All of the crucian carp, Carassius auratus and 50% of common carp. Cyprinus carpio examined in this study were infected with the leeches, Limnotrachelobdella sinensis. Especially, the infection of C. carpio with L. sinensis was the first report in Korea. The gill of C. auratus showed increased hydrophic degeneration of epithelial cell in the filament, blood congestion, hyperplasia of epithelial cell in the filament and lamellae. In the SEM observation, gill filament was transformed to the cylinder form by the lamellae fusion. The lamellae surface showed degeneration, fragmentation of microridges. The extracellular cartilaginous matrix of the filaments was exposed by the collapse of epidermal layer. In the 18S rRNA analysis of L. sinensis, the relationships among these groups are not clear and not concord with their morphological classification.