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Tumor-infiltrated CD4+Foxp3+Treg cells improve tumor-associated macrophages polarization via adenosine/A2AR pathway

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Tumor-infiltrated CD4+Foxp3+Treg cells improve tumor-associa...

第十四届全国免疫学学术大会

作者： Jianlei Xing Yichen Zhou Li Zhang Congcong Zhou Yifan Xia Jinyan Wang Department of Immunology China Medical University

CD4Foxp3Treg cells are essential to maintain self-tolerance and immune suppression of inflammatory *** accumulated evidence has shown that increased frequency and inhibition of CD4Foxp3Treg cells contribute to the tumor growth and progression in a variety of cancers,including lung cancer,highlighting the crucial role of CD4Foxp3Treg cells in the development of ***-associated macrophages(TAMs) are the most abundant immune cells in tumor microenvironment during different stages of diverse solid cancers *** has been demonstrated that TAMs display highly functional plasticity undergoing polarization during tumor growth and ***,M1 cells are able to exert anti-tumor immunity to suppress tumor development,based on the fact that M1 cells can be characterized by phagocytosis and antigen presentation capacity thus inflammatory cytokines including TNF,IL-1 and IL-6 can be *** contrast,M2 cells exert protumoral functions by generating inhibitory cytokines and mediators,such as IL-1 0,VEGF and MMP-9,enhancing tumor growth,angiogenesis,invasion and *** study has suggested that polarization of pro-tumoral M2 cells is a dynamic process involving both intrinsic and extrinsic factors in tumor ***,the mechanism extrinsically underlying TAMs polarization in tumor microenvironment is yet to be ***,we hypothesized that increased frequency of CD4Foxp3Treg cells may closely interact with TAMs and contribute to M2 polarization,thus promoting tumor growth,invasion and metastasisof *** murine Lewis lung cancer model,we found that CD4Foxp3Treg cells play an essential role for LLC tumor growth and metastasis,closely associated with polarized M2-like cells in tumor microenvironment of LLC-bearing *** of CD4Foxp3Treg cells rescued M2-like cells into M1-like cells,inhibiting tumor growth,invasion and metastasis of LLC ***,we found that a substantial population

关键词： CD4+Foxp3+Treg Tumor associated Macrophage adenosine A2AR

Thermochemistry of Heteroatomic Compounds: the Heats of Combustion and Formation of Glycoside and adenosine Phosphates

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International Journal of Organic Chemistry 2011年第3期1卷 67-70页

作者： Vitaly Ovchinnikov Ludmila Lapteva 不详

The heats of combustion of 4th glycoside in the condensed state with the use of the equation ΔcombH=15.7-117.2(N-g) , in which N is a number bond-forming (valence) electrons less the number (g) of lone electron pairs of nitrogen (g = 1) and oxygen (g = 2), have been determined. Such dependence is deduced previously joint for the description of the combustion enthalpies of 17 simple ethers of a cyclic structure and different sugars. The heats of formation ( ΔfHo ) of the mentioned above glycosides were calculated according to the Hess law via two ways: 1) through the use their heats of hydrolysis ( ΔhydrH ), which have been investigated earlier experimentally, 2) with the use the calculated the heats of combustion. The last procedure has been used also for the calculation of the heats of formation of the adenosine tri(ATP)-, di(ADP)- and mono(AMP)phosphates because of such thermochemical parameter is often hard achieved experimentally. The heats of hydrolysis ( ΔfH°hydr ) of ATP into ADP and ADP into AMP were calculated on the basis of their heats of formation in water ( ΔfH°aq ). The free energies of the same process ( ΔhydrG ) were known in literature. Last circumstance give us a possibility to calculate the hydrolysis entropies ( ΔhydrS ) using the Gibbs equation. The entropy values are a large negative, that pointed on the preliminary complex formation between adenosine phosphates and water before the breaking of P-O bonds or P-O-C fragments in its.

关键词： Glycoside Phosphates adenosine Phosphates Heat of Combustion Heat of Formation

Dipyridamole enhances inhibitory effect of adenosine on neutrophils in human peripheral blood

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Journal of Nanjing Medical University 2008年第4期22卷 243-245页

作者： Yu Zhang Qingyan Zhang Jing Zhang Qian Tian minghua Li Department of Cardiology the First Hospital of Jilin University Changchunl 30021 Jilin Province China

Objective： It was known that neutrophils play an important role in ischemic-reperfusion injury. In this study we tested the effect and its mechanism of dipyfidamole on neutrophils. Methods：Hydrogen peroxide（H2O2） production by neutrophils was determined using luminol amplified chemiluminescence and the percentage of activity was calculated by observing the uninhibited peak height. Results： Dipyfidamole per se produced a concentration-dependent inhibition of H2O2 by formyl-MetleuPhe（fMLP）-stimulated neutrophils. Dipyridamole at a low concentration（0.3 μ mol · L^-1） that per se affected neutrophils only slightly, enhanced markedly the effects of adenosine on neutrophils. On the other hand, dipyfidamole did not alter the inhibitory effect of NECA（5＇ -N-ethylcarboxamidoadenosine） on neutrophils. However, propentofylline, a known inhibitor of adenosine uptake, also gotten the same result. Conclusion：Dipyfidamole inhibited the production of H2O2 by fMLP-sfimulated neutrophils. Dipyfidamole at a low concentration enhanced the inhibitory effect of adenosine on neutrophils. The mechanism involved is probably due to the effect of dipyfidamole on adenosine uptake.

关键词： dipyridamole hydrogen peroxide adenosine neutrophils

Anticancer effect of adenosine on gastric cancer via diverse signaling pathways

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World Journal of Gastroenterology 2015年第39期21卷 10931-10935页

作者： Ayako Tsuchiya Tomoyuki Nishizaki Division of Bioin- formation Department of Physiology Hyogo College of Medicine

Extracellular adenosine induces apoptosis in a variety of cancer cells via intrinsic and extrinsic pathways. In the former pathway, adenosine uptake into cells triggers apoptosis, and in the latter pathway, adenosine receptors mediate apoptosis. Extracellular adenosine also inducesapoptosis of gastric cancer cells. Extracellular adenosine is transported into cells through an adenosine transporter and converted to AMP by adenosine kinase. In turn, AMP activates AMP-activated protein kinase(AMPK). AMPK is the factor responsible for caspase-independent apoptosis of GT3-TKB gastric cancer cells. Extracellular adenosine, on the other hand, induces caspase-dependent apoptosis of MKN28 and MKN45 gastric cancer cells by two mechanisms. Firstly, AMP, converted from intracellularly transported adenosine, initiates apoptosis, regardless of AMPK. Secondly, the A3 adenosine receptor, linked to Gi/Gq proteins, mediates apoptosis by activating the Gq protein effector, phospholipase Cγ, to produce inositol 1,4,5-trisphosphate and diacylglycerol, which activate protein kinase C. Consequently, the mechanisms underlying adenosine-induced apoptosis vary, depending upon gastric cancer cell types. Understand the contribution of each downstream target molecule of adenosine to apoptosis induction may aid the establishment of tailor-made chemotherapy for gastric cancer.

关键词： adenosine Apoptosis Intrinsic pathway Extrinsic pa

<i>Cordyceps sinensis</i>Acts As an adenosine A<sub>3</sub>Receptor Agonist on Mouse Melanoma and Lung Carcinoma Cells, and Human Fibrosarcoma and Colon Carcinoma Cells

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Pharmacology & Pharmacy 2011年第4期2卷 266-270页

作者： Noriko Yoshikawa Arisa Nishiuchi Erika Kubo Yu Yamaguchi Masaru Kunitomo Satomi Kagota Kazumasa Shinozuka Kazuki Nakamura 不详

Cordyceps sinensis, a parasitic fungus on the larva of Lapidoptera, has been used as a traditional Chinese medicine. We previously reported that the growth of B16-BL6 mouse melanoma (B16-BL6) cells and mouse Lewis lung carcinoma (LLC) cells was inhibited by cordycepin (3’-deoxyadenosine), an ingredient of Cordyceps sinensis, and its effect was antagonized by MRS1191, a selective adenosine A3 receptor (A3-R) antagonist although adenosine (up to 100 μM) had no effect on the growth of B16-BL6 and LLC cells. In this study, we investigated whether water extracts of Cordyceps sinensis (WECS) inhibit the growth of B16-BL6 cells, LLC cells, HT1080 human fibrosarcoma (HT1080) cells and CW-2 human colon carcinoma (CW-2) cells via their A3-R. As a result, the growth of all cell lines were potently inhibited by WECS (10 μg/mL) and the inhibitory effect of WECS was significantly antagonized by MRS1191 (1 μM). Furthermore, WECS included 2.34% w/w cordycepin and 0.12% w/w adenosine as components according to the HPLC- ECD system. In conclusion, WECS inhibited the proliferation of four cancer cell lines by stimulation of A3-R and the main component in WECS with anticancer action might be cordycepin instead of adenosine.

关键词： Cordyceps Sinensis adenosine A3 Receptor Cordycepin HPLC-ECD

DETERMINATION OF CYCLIC adenosine MONOPHOSPHATE (cAMP) IN HOMOGENATES OF PARAGONIMUS WORMS

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Chinese Science Bulletin 1983年第6期28卷 832-834页

作者：张夏英钟惠澜熊军曹维霁高佩芝许炽标邵兰 Beijing Tropical Medicine Research Institute

It has long been known that cAMP is the second messenger in the metabolism of mammalians, plants and microbes, so we suppose that cAMP also has some important role in regulating the metabolism of parasites. An investigation on the role of cAMP in regulating the metabolism of parasites seems to have not only theoretical interest, but also practical value in the search for new therapeutic agents for parasitic diseases.

关键词： metabolism regulating microbes parasitic suppose monophosphate messenger adenosine blank hormones

Development and application of a liquid chromatographic method for analysis of adenosine in royal jelly

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Development and application of a liquid chromatographic meth...

二十一世纪第二届全国蜂业科技与蜂产业发展大会

作者：吴黎明 Liang Hu Fu Jing Zhao Xiao Zhou Jin Hui Zhou Li Yi Xiao Feng Xue Research Institute Chinese Academy of Agricultural Sciences Bee College of Animal Sciences Zhejiang University

A simple method is described for the determination of adenosine in royal *** adenosine in the sample was extracted using 80% ethanol and analyzed by reversed-phase liquid *** separation was performed using a Dionex HPLC system with a Waters Symmetry C18 column,and with 0.4% phosphoric acid and methanol gradient *** average recoveries were 91.6% to 98.3%（n=6）with standard deviation below 5.3%.The limits of detection and quantification were 1.2 mg/kg and 4.1 mg/kg,*** developed method has been successfully applied to analyze royal jelly *** 45 royal jelly products,the adenosine content varied from 5.9 to 2057.4 mg/kg.

关键词： adenosine Royal jelly HPLC

Chronic morphine treatment impaired hippocampal long-term potentiation and spatial memory via accumulation of extracellular adenosine acting on adenosine Al receptors

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Chronic morphine treatment impaired hippocampal long-term po...

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Gang LU~1,Qi-Xin ZHOU~2,Shuo KANG~1,Lin XU~2,Jing-Gen LIU~(1,*) 1 State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Shanghai Institute For Biological Sciences,Chinese Academy of Sciences,Shanghai 201203,China 2 Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province,Kunming Institute of Zoology,Kunming 650223,China

＜正＞Chronic exposure to opiates impairs hippocampal long-term potentiation（LTP） and spatial memory, but the underlying mechanisms remain to be *** the well known effects of adenosine,an important neuromodulator,on hippocampal neuronal excitability and synaptic plasticity,we investigated the potential effect of changes in adenosine concentrations on chronic morphine treatment-induced impairment of hippocampal CA1 LTP and spatial *** found that chronic treatment in mice with either increasing doses（20-100 mg/kg） of morphine for 7 d or equal daily dose（20 mg/kg） of morphine for 12 d led to a significant increase of hippocampal extracellular adenosine ***,we found that accumulated adenosine contributed to the inhibition of the hippocampal CA1 LTP and impairment of spatial memory retrieval measured in the Morris water *** A1 receptor antagonist 8-cyclopenty1-1,3-dipropylxanthine significantly reversed chronic morphine-induced impairment of hippocampal CA1 LTP and spatial ***,adenosine deaminase,which converts adenosine into the inactive metabolite inosine,restored impaired hippocampal CA1 *** further found that adenosine accumulation was attributable to the alteration of adenosine uptake but not adenosine *** nucleoside transporters（ENT2） appeared to play a key role in the reduction of adenosine *** in PKC-α/βactivity were correlated with the attenuation of the ENT2 function in the short-term（2 h） but not in the long-term（7 d） period after the termination of morphine *** study reveals a potential mechanism by which chronic exposure to morphine leads to impairment of both hippocampal LTP and spatial memory.

关键词： morphine spatial memory adenosine PKC LTP ENT

The Limiting Effect of α-adrenergic Vasoconstriction on Canine Coronary Vasodilation Induced by adenosine

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Journal of Medical Colleges of PLA(China) 1989年第2期4卷 174-177页

作者：孙建中李之源王跃民臧益民王复周 Department of Physiology Fourth Military Medical UniversityXi'an

This study examines the effects of x-adrenergic stimulation on coronaryvasodilation induced by selective doses of intracoronary *** anesthetized open-chest dogs,the left anterior descending coronary artery（LAD）was perfused at a constant flow and its perfusionpressure was measured,pr ctolol（2.5 mg）was infused into the LAD to block β1-adrenergicreceptors in the *** adenosine at increasing doses produced graded decreasesin coronary vascular resistance by 8.7%（2μg/min）,20.6%（10/μg/min）and 28%（50 μg/min）of the *** doses（6μg）of intracoronary norepinephfine produced increases in coronaryvascular resistance by 17.4%（adenosine 2 μg/min）,23.2%（adenosine 10μg/min）and 34.1%（adenosine 50 μg/min）of the control when coronary vessels were dilated by increasing doses ofadenosine,*** is suggested that the constrictive effect of x-adrenergic stimulalion can ex-ert a limiting effect on adenosine-induced coronary vasodilation.

关键词： norepinephrine adenosine coronary artery