• Title, Summary, Keyword: EC-Mechanism

Search Result 151, Processing Time 0.036 seconds

Regulation of IL-6 signaling by miR-125a and let-7e in endothelial cells controls vasculogenic mimicry formation of breast cancer cells

  • Park, Youngsook;Kim, Jongmin
    • BMB Reports
    • /
    • v.52 no.3
    • /
    • pp.214-219
    • /
    • 2019
  • The role of tumor-proximal factors in tumor plasticity during chemoresistance and metastasis following chemotherapy is well studied. However, the role of endothelial cell (EC) derived paracrine factors in tumor plasticity, their effect on chemotherapeutic outcome, and the mechanism by which these paracrine factors modulate the tumor microenvironment are not well understood. In this study, we report a novel mechanism by which endothelial miR-125a and let-7e-mediated regulation of interleukin-6 (IL-6) signaling can manipulate vasculogenic mimicry (VM) formation of MDA-MB-231 breast cancer cells. We found that endothelial IL-6 levels were significantly higher in response to cisplatin treatment, whereas levels of IL-6 upon cisplatin exposure remained unchanged in MDA-MB-231 breast cancer cells. We additionally found an inverse correlation between IL-6 and miR-125a/let-7e expression levels in cisplatin treated ECs. Interestingly, IL-6, IL-6 receptor (IL-6R), and signal transducer and activator of transcription 3 (STAT3) genes in the IL-6 pathway are closely regulated by miR-125a and let-7e, which directly target its 3' untranslated region. Functional analyses revealed that endothelial miR-125a and let-7e inhibit IL-6-induced adhesion of monocytes to ECs. Furthermore, conditioned medium from cisplatin treated ECs induced a significantly higher formation of VM in MDA-MB-231 breast cancer cells as compared to that from intact ECs; this effect of cisplatin treatment was abrogated by concurrent overexpression of miR-125a and let-7e. Overall, this study reveals a novel EC-tumor cell crosstalk mediated by the endothelial miR-125a/let-7e-IL-6 signaling axis, which might improve chemosensitivity and provide potential therapeutic targets for the treatment of cancer.

Hemorrhagic Moyamoya Disease : A Recent Update

  • Fujimura, Miki;Tominaga, Teiji
    • Journal of Korean Neurosurgical Society
    • /
    • v.62 no.2
    • /
    • pp.136-143
    • /
    • 2019
  • Moyamoya disease (MMD) is a progressive cerebrovascular disease with unknown etiology, characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network formation at the base of the brain. MMD has an intrinsic nature to convert the vascular supply for the brain from internal carotid (IC) system to the external carotid (EC) system, as indicated by Suzuki's angiographic staging. Insufficiency of this 'IC-EC conversion system' could result not only in cerebral ischemia, but also in intracranial hemorrhage from inadequate collateral anastomosis, both of which represent the clinical manifestation of MMD. Surgical revascularization prevents cerebral ischemic attack by improving cerebral blood flow, and recent evidence further suggests that extracranial-intracranial bypass could powerfully reduce the risk of re-bleeding in MMD patients with posterior hemorrhage, who were known to have extremely high re-bleeding risk. Although the exact mechanism underlying the hemorrhagic presentation in MMD is undetermined, most recent angiographic analysis revealed the characteristic angio-architecture related to high re-bleeding risk, such as the extension and dilatation of choroidal collaterals and posterior cerebral artery involvement. We sought to update the current management strategy for hemorrhagic MMD, including the outcome of surgical revascularization for hemorrhagic MMD in our institute. Further investigations will clarify the optimal surgical strategy to prevent hemorrhagic manifestation in patients with MMD.

Electrochemical Reduction of 0,0-Dimethyl-0-(3-Methyl-4-Nitrophenyl)-phosphorothioate(Sumithion®) in Acetonitrile Solution (Acetonitrile 용액중(溶液中)에서 0,0-Dimethyl-0-(3-Methyl-4-Nitrophenyl)-phosphorothioate(Sumithion®)의 전기화학적(電氣化學的) 환원반응(還元反應))

  • Park, Seung Heui;Sung, Nack Do
    • Korean Journal of Agricultural Science
    • /
    • v.11 no.2
    • /
    • pp.315-321
    • /
    • 1984
  • The electrochemical reduction of 0,0-dimethyl-0-(3-methyl-4 -nitrophenyl)-phosphorothioate ($Sumithion^{(R)}$) in acetonitrile solution has been studied by direct current (DC), differential pulse (DP) polarography and cyclic voltammetry methods. The irreversible electron-transfer chemical reaction (EC) mechanism of Sumithion proceeds by six electron-transfer to form radical and reduction of three-step which undergoes single bond of the phosphorus atom & phenoxy group by electron-transfer and protonation cleaved to give p-hydroxyamino-m-cresol and dimethylthiophosphonate as major product.

  • PDF

Electrochemical Study on the 3-Phenyl-4-Nitrosydnone (3-Phenyl-4-Nitrosydnone의 전기화학적 연구)

  • Il-Kwang Kim;Youn-Geun Kim;Soon-Jong Han
    • Journal of the Korean Chemical Society
    • /
    • v.32 no.3
    • /
    • pp.195-202
    • /
    • 1988
  • An electrochemical reduction on the 3-phenyl-4-nitrosydnone in acetonitrile solution has been studied by direct current, differential pulse polarography, cyclic voltammetry and controlled potential coulometry. Before the cleavage of phenyl-N single bond a irreversible electron transfer-chemical reaction(EC) mechanism of nitro functional group proceeded to form amino (or-hydroxylamino) group by multielectron transfer which is followed to give phenyl hydrazine by single electron transfer-chemical reaction at the 2nd and 3rd irreversible reduction wave of high negative potential region. The cathodic half-wave potentials shown to be shift negative due to inhibitory effect of cetyl-trimethyl ammonium bromide micelle while reversible anodic peaks on the 2nd and 3rd reduction waves in the presence of NaLS at high negative potential region.

  • PDF

Effects of Novel Potassium Channel Opener KR-30450 and its Metabolite KR-30818 on the Smooth, Muscle of the Guinea Pig

  • Jung, Yi-Sook;Moon, Chang-Hyun;Yoo, Sung-Eun;Shin, Hwa-Sup
    • Biomolecules & Therapeutics
    • /
    • v.4 no.4
    • /
    • pp.373-377
    • /
    • 1996
  • The effect of potassium channel openers, KR-30450, KR-30818 and lemakalim have been compared against several spasmogens in guinea pig bronchi. In guinea pig bronchi, KR-30450 had a greater relaxant effect than lemakalim and KR-30818 against tone induced by histamine $10^{-5}M$ ($EC_{50}$ $\mu$M: KR-30450, 0.108$\pm$0.077; KR-30818, 0.403$\pm$0.023; lemakalim, 0.968$\pm$0.036) and prostaglandin $F_{2\alpha} 3\times10^{-6} M$ ($EC_{50}$ $\mu$M: KR-30450, 0.018$\pm$0.001; KR-30818, 0.028$\pm$0.003; lemakalim, 0.138$\pm$0.019). Relaxant effect of KR-30450 and KR-30818 were significantly reduced by 20 min pretreatment of tissues with $10^[-6}$ M glibenclamide, a selective blocker of ATP-sensitive potassium channel. Against acetylcholine-induced tone in guinea pig bronchi, however, these compounds had little effect. In summary, KR-30450 and KR-30818 showed greater relaxant effect than lemakalim in guinea pig bronchi (KR-30450>KR-30818>lemakalim). These relaxant actions are suggested to be mediated at least in part by a mechanism which involves the opening of ATP-sensitive potassium channel.

  • PDF

Effect of Purified Green Tea Catechins on Cytosolic Phospholipase $A_2$ and Arachidonic Acid Release in Human Gastrointestinal Cancer Cell Lines

  • Hong, Jung-Il;Yang, Chung-S.
    • Food Science and Biotechnology
    • /
    • v.15 no.5
    • /
    • pp.799-804
    • /
    • 2006
  • Ingestion of green tea has been shown to decrease prostaglandin $E_2$ levels in human colorectum, suggesting that tea constituents modulate arachidonic acid metabolism. In the present study, we investigated the effects of four purified green tea catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG), and (-)-epicatechin-3-gallate (ECG), on the catalytic activity of cytosolic phospholipase $A_2$ ($cPLA_2$) and release of arachidonic acid and its metabolites from intact cells. At $50\;{\mu}M$, EGCG and ECG inhibited $cPLA_2$ activity by 19 and 37%, respectively, whereas EC and EGC were less effective. The inhibitory effects of these catechins on arachidonic acid metabolism in intact cells were much more pronounced. At $10\;{\mu}M$, EGCG and ECG inhibited the release of arachidonic acid and its metabolites by 50-70% in human colon adenocarcinoma cells (HT-29) and human esophageal squamous carcinoma cells (KYSE-190 and 450). EGCG and ECG also inhibited arachidonic acid release induced by A23187, a calcium ionophore, in both HT-29 and KYSE-450 cell lines by 30-50%. The inhibitory effects of green tea catechins on $cPLA_2$ and arachidonic acid release may provide a possible mechanism for the prevention of human gastrointestinal inflammation and cancers.

Growth Inhibition and G2/M Phase Cell Cycle Arrest by 3,4,5-Trimethoxy-4'-bromo-cis-stilbene in Human Colon Cancer Cells

  • Heo, Yeon-Hoi;Min, Hye-Young;Kim, Sang-Hee;Lee, Sang-Kook
    • Biomolecules & Therapeutics
    • /
    • v.15 no.2
    • /
    • pp.95-101
    • /
    • 2007
  • Resveratrol (3,5,4’-trihydroxy-trans-stilbene), a naturally occurring phytoallexin abundant in grapes and several plants, has been shown to be active in inhibiting proliferation and inducing apoptosis in several human cancer cell lines. On the line of the biological activity of resveratrol, a variety of resveratrol analogs were synthesized and evaluated for their growth inhibitory effects against several human cancer cell lines. In the present study, we found that one of the resveratrol analogs, 3,4,5-trimethoxy-4’-bromo-cis-stilbene, markedly suppressed human colon cancer cell proliferation (EC$_{50}$ = 0.01 ${\mu}$g/ml), and the inhibitory activity was superior to its corresponding trans-isomer (EC$_{50}$ = 1.6 ${\mu}$g/ml) and resveratrol (EC$_{50}$ = 18.7 ${\mu}$g/ml). Prompted by the strong growth inhibitory activity in cultured human colon cancer cells (Col2), we investigated its mechanism of action. 3,4,5-Trimethoxy-4’-bromo-cis-stilbene induced arrest of cell cycle progression at G2/M phase and increased at sub-G1 phase DNA contents of the cell cycle in a time- and dose-dependent manner. Colony formation was also inhibited in a dose-dependent manner, indicating the inhibitory activity of the compound on cell proliferation. Moreover, the morphological changes and condensation of the cellular DNA by the treatment of the compound were well correlated with the induction of apoptosis. These data suggest the potential of 3,4,5-trimethoxy-4’-bromo-cis-stilbene might serve as a cancer chemotherapeutic or chemopreventive agent by virtue of arresting the cell cycle and inducing apoptosis for the human colon cancer cells.

Comparative Investigation of Glutathione S-Transferases, Glyoxalase-I and Alliinase Activities in Different Vegetable Crops

  • Hossain, Md Daud;Rohman, Md Motiar;Fujita, Masayuki
    • Journal of Crop Science and Biotechnology
    • /
    • v.10 no.1
    • /
    • pp.19-26
    • /
    • 2007
  • Glutathione S-transferases(GSTs, EC 2.5.1.18), glyoxalase-I(EC 4.4.1.5) and alliin lyase(alliinase, EC 4.4.1.4) are important enzyme systems in plant bodies. The first two are mainly detoxifying enzymes that utilize glutathione(GSH) in the defense mechanism, and the last one is mainly involved in secondary metabolism and relevant to sulfur compounds derived from GSH. The activities of the three enzymes have been investigated in soluble extracts of vegetable crops, including pumpkin, cabbage, broccoli, radish, carrot, potato, sweet potato, mungbean, and onion. GST activities were detected in all of the vegetables, and the extract of onion bulb exhibited the highest specific activity(648 nmol/min/mgP). The putative GSTs of most of the vegetables were found to be induced by ethanol. The activities of GSTs in onion bulb were found to be markedly inhibited by S-hexyl glutathione and were also inhibited by S-butyl glutathione and S-propyl glutathione. The anti-CmGSTF1 antiserum recognized a thick band for putative onion GST. The estimated glyoxalase-I activity level was also high in onion bulb(4540 nmol/min/mgP), indicating that the thick band detected by Western blot analysis might result from partial recognition of glyoxalase-I by the antiserum. The specific activities for glyoxalase-I were moderate in radish and carrot, and the extracts of other vegetables had rather low levels of activities. The extract of onion also showed the highest specific activity level for alliinase(2069nmol pyruvate/mgP). The extracts of other vegetables also had alliinase activities, although the estimated values were much lower than that of onion.

  • PDF

A Study of Business Model Based on Intelligent Agents for Optimal Contract (최적의 매매계약을 위한 지능형 에이전트 기반의 비즈니스 모형에 관한 연구)

  • 정종진
    • Journal of the Korea Computer Industry Society
    • /
    • v.5 no.1
    • /
    • pp.131-146
    • /
    • 2004
  • As Electronic Commerce(EC) has been emerged and has developed, many researchers have tried to establish EC framework for automated contract and negotiation using agent technologies. Traditional researches, however, often had limitations. They often enforced the user's participations during the automated contract process of agents. They also could only consider a few of the user's requirements for a specific goods and did not have supported the procedures and methodologies for making the best contract. In this paper, we propose business model on EC based on multiagents to overcome the defects of the previous researches. We apply CSP techniques to brokerage process to satisfy various preferential requirements from the user. We also propose efficient negotiation mechanism using negotiation model of game theory. The contract candidates automatically negotiate and mediate in terms of their benefits through the proposed negotiation mechanism. For the optimal brokerage and automated negotiation, the agents process activities for contract on three layers, which are called competition layer, constraint satisfaction layer and negotiation layer in the proposed model. We also design the message driven communication protocol to support the automated contract among the agents. Finally, we have implemented prototype systems applying the proposed model and have shown the various experimental results for efficiency of the proposed model.

  • PDF

Extracellular $K^+$ Effects on the Mouse Aortic Endothelial Cell Contractility (쥐 대동맥 혈관 내피세포에서 세포 외 $K^+$에 의한 혈관 수축선 조절 기전)

  • 안재호;유지영
    • The Korean Journal of Thoracic and Cardiovascular Surgery
    • /
    • v.36 no.12
    • /
    • pp.887-893
    • /
    • 2003
  • External stimuli increases intracellular (IC) $Ca^{2+}$, which increases extracellular (EC) $K^{+}$. To verify $K^{+}$ effects on the vascular contraction, we performed an experiment using mouse aortic endothelial cell. Meterial and Method: We examined the mouse aortic contractility changes as we measured the IC $Ca^{2+}$ change and ionic current by using the voltage clamp technique under different conditions such as: increasing EC $K^{+}$, removing endothelial cell, giving L-NAME (N-nitro-L-arginine methyl ester) which suppress nitric oxide formation, Ouabain which control N $a^{+}$ - $K^{+}$ pump and N $i^{2+}$ which repress N $a^{+}$-C $a^{2+}$ exchanger Result: When we increased EC $K^{+}$ from 6 to 12 mM, there was no change in aortic contractility. Aorta contracted with more than 12 mM of EC $K^{+}$. Ace-tylcholine (ACh) induced relaxation was inhibited with EC $K^{+}$ from 6 to 12 mM, but was not found after de-endothelialization or L-NAME treatment. ATP or ACh increased IC $Ca^{2+}$ in cultured endothelium. After maximal increase of IC $Ca^{2+}$, increasing EC $K^{+}$ from 6 to 12 mM made IC $Ca^{2+}$ decrease and re-decreasing EC $K^{+}$ to 6 mM made IC $Ca^{2+}$ increase. Ouabain and N $i^{2+}$ masked the inhibitory effect of endothelium dependent relaxation by increased EC $K^{+}$. Conclusion: These data indicate that increase in EC $K^{+}$ relaxes vascular smooth muscle and reduces $Ca^{2+}$ in the endothelial cells which inhibit endothelium dependent relaxation. This inhibitory mechanism may be due to the activation of N $a^{+}$- $K^{+}$ pump and N $a^{+}$-C $a^{2+}$ exchanger. $a^{+}$-C $a^{2+}$ exchanger.r.