• Title/Summary/Keyword: Leukemia cell

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Delayed Human Neutrophil Apoptosis by Trichomonas vaginalis Lysate

  • Song, Hyun-Ouk;Lim, Young-Su;Moon, Sun-Joo;Ahn, Myoung-Hee;Ryu, Jae-Sook
    • Parasites, Hosts and Diseases
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    • v.48 no.1
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    • pp.1-7
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    • 2010
  • Neutrophils play an important role in the human immune system for protection against such microorganisms as a protozoan parasite, Trichomonas vaginalis; however, the precise role of neutrophils in the pathogenesis of trichomoniasis is still unknown. Moreover, it is thought that trichomonal lysates and excretory-secretory products (ESP), as well as live T. vaginalis, could possibly interact with neutrophils in local tissues, including areas of inflammation induced by T. vaginalis in humans. The aim of this study was to investigate the influence of T. vaginalis lysate on the fate of neutrophils. We found that T. vaginalis lysate inhibits apoptosis of human neutrophils as revealed by Giemsa stain. Less altered mitochondrial membrane potential (MMP) and surface CD16 receptor expression also supported the idea that neutrophil apoptosis is delayed after T. vaginalis lysate stimulation. In contrast, ESP stimulated-neutrophils were similar in apoptotic features of untreated neutrophils. Maintained caspase-3 and myeloid cell leukemia-1 (Mcl-1) in neutrophils co-cultured with trichomonad lysate suggest that an intrinsic mitochondrial pathway of apoptosis was involved in T. vaginalis lysate-induced delayed neutrophil apoptosis; this phenomenon may contribute to local inflammation in trichomoniasis.

Inhibitory Effect of Paeoniflorin on Fos-Jun-DNA Complex Formation and Stimulation of Apoptosis in HL-60 Cells

  • Kwon, Hae-Young;Kim, Kyoung-Su;Park, Se-Yeon;Lee, Dug-Keun;Yang, Chul-Hak
    • BMB Reports
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    • v.34 no.1
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    • pp.28-32
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    • 2001
  • The Fos-Jun heterodimers are part of the regulatory network of gene expression and nuclear proteins encoded by proto-oncogenes. The activation of Fos-Jun is important in the transmission of the tumor-promoting signal from the extracellular environment to the nuclear transcription mechanism. To search for the inhibitors of the Fos-Jun DNA complex formation, several natural products were screened and water-soluble paeoniflorin reduced the binding activity of the Fos-Jun heterodimer. This active compound was purified by silica gel column chromatography and HPLC. The electrophoresis mobility shift assay and reverse-phase HPLC test showed that paeoniflorin reduced the AP-l function. The cytotoxic effect of paeoniflorin was observed in HL-60. These results indicate that paeoniflorin blocks the Fos-Jun heterodimer-binding site of the AP-l DNA and it also has cytotoxic effects on human leukemia cell lines.

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Inhibition of Apoptosis is Responsible for the Acquired Resistance of K562 Cells to Cisplatin

  • Lee, Soo-Yong;Kim, Dong-Hyun
    • Biomolecules & Therapeutics
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    • v.12 no.2
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    • pp.85-91
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    • 2004
  • In all attempt to elucidate the role of apoptosis in drug resistance, cisplatin-resistant human chronic myelogenous leukemia (CML) K562 cells (K562/CDDP) were established and compared with drug sensitive parent cells (K562) in the induction of apoptosis. K562/CDDP cells were 5-fold more resistant to cisplatin compared to K562 cells. In addition, K562/CDDP cells were significantly more resistant to apoptois as judged by DNA fragmentation and DAPI staining. K562/CDDP cells exhibited decreased proleolytic activity of caspase-3 and this was further demonstrated by decreased cleavage of its substrate poly (ADP-ribose) polymerase (PARR- Western blot analysis showed that K562/CDDP cells had longer sustained levels of BCL-$X_L$ whereas no difference was noted in the level of Bcl-2. the translocation of Bax to mitochondria was significantly delayed in K562/CDDP cells. These results suggest that the reduced translocation of Bax and the sustained expression of BCL-$X_L$ may cause resistance to apoptosis through prevention of mitochondria release of cytochrome c, which subsequently induces reduction of caspase-3 activity and that this response is partly responsible for the acquired resistance to cisplatin ill K562 cells.

Cellular Signaling Molecules Associated with Peptidoglycan-Induced CCL3 Up-Regulation

  • Kim, Kang-Seung;Rhim, Byung-Yong;Eo, Seong-Kug;Kim, Koan-Hoi
    • Biomolecules & Therapeutics
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    • v.19 no.3
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    • pp.302-307
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    • 2011
  • Peptidoglycan (PGN) is detected in inflammatory cell-rich regions of human atheromatous plaques. The present study investigated the effects of PGN on CC chemokine ligand 3 (CCL3) expression, which is elevated in the atherosclerotic arteries, and determined cellular factors involved in PGN-mediated CCL3 up-regulation in mononuclear cells, with the goal of understanding the molecular mechanisms of inflammatory responses to bacterial pathogen-associated molecular patterns in diseased arteries. Exposure of human monocytic leukemia THP-1 cells to PGN resulted in enhanced secretion of CCL3 and profound induction of the CCL3 gene transcript. Both events were abrogated by oxidized 1-palmitoyl-2-arachidonosyl-sn-phosphatidylcholine, an inhibitor of Toll-like receptors 2/4. Pharmacological inhibitors such as U0126, SP6001250, Akt inhibitor IV, rapamycin, RO318220, diphenyleneiodonium chloride, and N-acetylcysteine also significantly attenuated PGN-mediated CCL3 up-regulation. However, polymyxin B, LY294002, and SB202190 did not influence CCL3 expression. We propose that PGN contributes to enhanced CCL3 expression in atherosclerotic plaques and that Toll-like receptors (TLR2), Akt, mTOR, mitogen-activated protein kinase, and reactive oxygen species are involved in that process.

The Effect of Lipopolysaccharide on Noxa Expression Is Mediated through IRF1, 3, and 7

  • Piya, Sujan;Kim, Tae-Hyoung
    • Journal of Microbiology and Biotechnology
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    • v.28 no.3
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    • pp.491-497
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    • 2018
  • Lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria, elicits the secretion of cytokines, such as interferons, that stimulate the host defense system. Previously, we demonstrated that interferons induce interferon regulatory factors (IRFs) 1, 3, and 7, which regulate the transcription of Noxa and alter the expression profiles of Bcl-2 family proteins in tumors. However, the immediate consequences of LPS stimulation on Noxa and BH3 expression in tumor cells remain uncharacterized. In this study, we determined that LPS induced Noxa expression in CT26 cells. Furthermore, studies in HCT116 parental and HCT116 p53-deficient cells revealed that LPS-mediated Noxa was independent of p53. Meanwhile, IRF1, 3, and 7 in CT26, HCT116 parental, and HT116 p53-deficient cells were upregulated by LPS stimulation, suggesting that LPS induces the expression of these IRFs in a p53-independent manner. The responsiveness of IRF1, 3, 4, and 7 binding to the Noxa promoter region to LPS indicated that IRF1, 3, and 7 activated Noxa expression, whereas IRF4 repressed Noxa expression. Together, these results suggest that LPS directly affects Noxa expression in tumor cells through IRFs, implicating that it may contribute to LPS-induced tumor regression.

Herpes Zoster Ophthalmicus in a Patient with Malignant Lymphoma (악성림프종 환자에서 발생한 안부 대상포진)

  • Lee, Jun-Hak;Kim, Hyung-Tae;Park, Jun-Beom;Park, Sang-Cheol;Kwon, Young-Eun
    • Journal of Hospice and Palliative Care
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    • v.8 no.1
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    • pp.52-56
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    • 2005
  • Herpes zoster (HZ) is an acute infection of the unilateral sensory dermatome caused by varicella-zoster virus (VZV) and is characterized by vesicular eruption and unilateral pain along the involved dermatome. Although the pathogenesis of HZ is incompletely understood, it is thought that when cell-mediated immunity falls below a critical level, dormant VZV within cells of the sensory ganglia are allowed to replicate and infect the host with the resultant clinical presentation of HZ. It has been associated with immunosuppressed states, such as advanced age, leukemia, lymphoma, chemotherapy and/or radiation treatment. We present a case of a 62-year-old female patient with malignant lymphoma suffering herpes zoster ophthalmicus who did not respond to conventional treatment, and in whom the application of various nerve blocks and patient-controlled analgesia produced moderate pain relief. The patient died twenty days later due to cardiopulmonary failure.

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Clinical Significance of Basal-like Breast Cancer in Chinese Women in Heilongjiang Province

  • Liu, Ying;Jiang, Qiu-Ying;Xin, Tao;Cai, Li;Zhao, Chang-Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2735-2738
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    • 2012
  • Background: Our objective was to clarify the clinical and biological characteristics of basal-like breast cancer (BLBC) and non-basal-like breast cancer (TN3BKE) in Heilongjiang. Methods: We examined, by immunohistochemistry, expression of biological markers cytokeratin (CK) 5/6 and epidermal growth factor receptor (EGFR) and B cell specific moloney murine leukemia virus integration site 1( Bmi-1) in triple-negative breast cancer (TNBC). We studied the correlation between BLBC and several factors related to tumor progression, along with its prognostic value. Results: In the 229 cases of operable TNBC, BLBC was detected in 178 (77.7%) and TN3BKE- in 51 (22.2%). There was no significant difference in clinicopathological factors between them, However, BLBC was significantly associated with Bmi-1 expression (P=0.000) and shorter disease-free survival (DFS) (P = 0.045) and overall survival (OS) (P = 0.041). Conclusions: Compared with the non-basal group, patients with BLBC have a high expression of Bmi-1 and a poor prognosis.

Inhibitory Effect of Galgeunhaegi-Tang on Compound48/80 Stimulated Allergic Reaction (갈근해기탕(葛根解肌湯)의 항 Allergy 및 항염증 효과)

  • Kim, Hyung-Kap;Shin, Sang-Woo;Park, Jong-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.2
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    • pp.381-388
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    • 2009
  • The present study was conducted to investigate the anti-allergic activity of Galgeunhaegi-Tang(GHT). We investigated the anti-allergic effects of GHT in RBL-2H3 basophilic leukemia cells by compound48/80, a mast cell degranulator and compound 48/80 induced anaphylactic shock in mice. GHT significantly inhibited ${\beta}$-hexosaminidase and histamine release from compound 48/80 stimulated RBL-2H3 cells. In addition, GHT effectively inhibited anaphylactic shock in mice by 40% at a dose 100 mg/mouse versus PBS treated control after the l.p injection(8 mg/kg) of compound 48/80. The in vitro anti-inflammatory activities of GHT in LPS-stimulated RAW 264.7 cells were investigated. GHT inhibited NO production in LPS-stimulated RAW 264.7 cells and effectively dowregulated the expression of iNOS mRNA and iNOS protein expression in LPS-stimulated RAW 264.7 cells. These result provide evidences that GHT may be beneficial in the treatment of allergic inflammtory disease.

A Study on the Thermal Analysis for the Robotic Arm of the Cord Blood Storage Tank (제대혈 용기 내부 로봇 암의 열해석에 관한 연구)

  • Yun, Sang-Kook;You, Sam-Sang
    • Journal of Advanced Marine Engineering and Technology
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    • v.32 no.5
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    • pp.724-729
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    • 2008
  • Umbilical cord blood has been recently considered an attractive potential alternative as a source of stem cell transplantation to curing diseases such as leukemia, cancers, immune disorders. Normally the stored system of the umbilical cord blood specimen is equipped with a computer-controlled robotic arm that enables the samples to locate the identification places in liquid nitrogen tank at regulated temperature as about $-196^{\circ}C$. As the half of robotic arm is in the air and the rest part is submerged in liquid nitrogen, the temperature of robotic arm varies from ambient to liquid nitrogen temperature. In this study the temperature variation of upper part of arm above tank lid was thermally analysed by using the commercial code of Ansys. The result of analysis was that the upper part of robotic arm was seriously frozen due to heat transfer from liquid nitrogen as low as -$120^{\circ}C$. In order to solve the frost problem of robotic arm, small PTFE tube block as resistance material was introduced into the lower part of tank lid instead of the whole stainless steel(SUS) robotic arm. The results showed that the temperature of robotic arm above the lid was higher enough, and this method would be one of the very effective measure to solve the problem.

A Combined Pharmacophore-Based Virtual Screening, Docking Study and Molecular Dynamics (MD) Simulation Approach to Identify Inhibitors with Novel Scaffolds for Myeloid cell leukemia (Mcl-1)

  • Bao, Guang-Kai;Zhou, Lu;Wang, Tai-Jin;He, Lu-Fen;Liu, Tao
    • Bulletin of the Korean Chemical Society
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    • v.35 no.7
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    • pp.2097-2108
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    • 2014
  • Chemical feature based quantitative pharmacophore models were generated using the HypoGen module implemented in DS2.5. The best hypothesis, Hypo1, which was characterized by the highest correlation coefficient (0.96), the highest cost difference (61.60) and the lowest RMSD (0.74), consisted of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic and one ring aromatic. The reliability of Hypo1 was validated on the basis of cost analysis, test set, Fischer's randomization method and GH test method. The validated Hypo1 was used as a 3D search query to identify novel inhibitors. The screened molecules were further refined by employing ADMET, docking studies and visual inspection. Three compounds with novel scaffolds were selected as the most promising candidates for the designing of Mcl-1 antagonists. Finally, a 10 ns molecular dynamics simulation was carried out on the complex of receptor and the retrieved ligand to demonstrate that the binding mode was stable during the MD simulation.