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Metabolic collaboration between cells in the tumor microenvironment has a negligible ef.ect on tumor growth

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The Innovation 2024年第2期5卷 107-114页

作者： Johan gustafsson f.riba Roshanzamir Anders Hagnestål Sagar M.Patel Oseeyi I.Daudu Donald f.Becker Jonathan L.Robinson Jens Nielsen Department of.Lif. Sciences Chalmers University of TechnologySE-41296 GothenburgSweden Hagnesia AB SE-43854 HindåsSweden Department of.Biochemistry and Redox Biology Center University of Nebraska-LincolnLincolnNE 68588USA BioInnovation Institute DK2200 CopenhagenDenmark

The tumor microenvironment is composed of.a complex mixture of.dif.erent cell types interacting under conditions of.nutrient deprivation,but the metabolism therein is not f.lly understood due to dif.iculties in measuring metabolic f.uxes and exchange of.metabolites between dif.erent cell types in ***-scale metabolic modeling enables estimation of.such exchange f.uxes as well as an opportunity to gain insight into the metabolic behavior of.individual cell ***,we estimated the availability of.nutrients and oxygen within the tumor microenvironment using concentration measurements f.om blood together with a metabolite dif.usion *** addition,we developed an approach to ef.iciently apply enzyme usage constraints in a comprehensive metabolic model of.human *** combined modeling reproduced severe hypoxic conditions and the Warburg ef.ect,and we f.und that limitations in enzymatic capacity contribute to cancer cells’pref.rential use of.glutamine as a substrate to the citric acid ***,we investigated the common hypothesis that some stromal cells are exploited by cancer cells to produce metabolites usef.l f.r the cancer *** identif.ed over 200 potential metabolites that could support collaboration between cancer cells and cancer-associated f.broblasts,but when limiting to metabolites previously identif.ed to participate in such collaboration,no growth advantage was *** work highlights the importance of.enzymatic capacity limitations f.r cell behaviors and exemplif.es the utility of.enzyme-constrained models f.r accurate prediction of.metabolism in cells and tumor microenvironments.

关键词： metabolism ef.ect limitations

稳定性慢性心力衰竭患者中NT-proBNP的长期临床变异

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世界核心医学期刊文摘（心脏病学分册） 2007年第7期3卷 42-43页

作者： Schou M. gustafsson f. Kjaer A. Hildebrandt P.R. 孙凯 Department of.Cardiology and Endocrinology Clinic E Frederiksberg University Hospital Ndr. Fasanvej 57-59 DK-2000 Frederiksberg Denmark

目的：评价稳定性慢性心力衰竭（CHf.患者中N-末端脑利钠肽前体（NT-proBNP）的长期临床变异。建议采用NT-proBNP来监测CHf.者尚需要NT-proBNP长期临床变异的精确资料。方法和结果：研究对象为在本心力衰竭诊疗中心接受治疗的患者，... 详细信息

目的：评价稳定性慢性心力衰竭（CHf.患者中N-末端脑利钠肽前体（NT-proBNP）的长期临床变异。建议采用NT-proBNP来监测CHf.者尚需要NT-proBNP长期临床变异的精确资料。方法和结果：研究对象为在本心力衰竭诊疗中心接受治疗的患者，记录随访1年和2年时的用药情况、生化指标和NYHA分级。仅将从第1次随访至第2次随访后12个月这一时期用药和NYHA分级无变化，亦未入院或死亡的患者纳入分析。共78例患者符合标准，年变异率为30％（中位值；极差0％～111％）（百分比变化范围：-87％～397％）。

关键词： NT-proBNP 慢性心力衰竭患者临床变异稳定性 NYHA分级用药情况 CHf.者脑利钠肽

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β受体阻滞剂在充血性心力衰竭治疗起始作用及药量调整过程中的耐受情况:随机对照研究

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世界核心医学期刊文摘（心脏病学分册） 2005年第3期1卷 22-23页

作者： Galatius S. gustafsson f. Atar D. Hildebrandt P.R. 高登峰 Department of.Cardiology P Gentofte University Hospital Niels Andersens vej 65 DK-2900 Hellerup Denmark Dr.

In clinical trials β-blockers(BB) are well tolerated in patients with systolic congestive heart f.ilure(CHf.. In contrast, in daily practice treatment initiation and titration appear to be more dif.icult and may dif.er in various BB-but systematic data are lacking. We randomized 87 patients with systolic CHf.mean age 70.1±10.6 years, 24%f.males, LVEf.0.28±0.10, NYHA Ⅲ-Ⅳ29%) to treatment with either bisoprolol or carvedilol, in order to assess and compare the maximally achievable number of.patients on treatment with these BB and the maximally achieved dosage during a minimum of.2 months attendance at our out patient heart f.ilure clinic. In those randomized to bisoprolol,mean dose at 2 months was 33%of.target dose (3.1±2.6 mg ) and 41%at discharge. In those on carvedilol, the mean dose at 2 months was 27%of.target dose(13.4±14.0 mg) and 32%at discharge. Thirty-nine and 40%of.the bisoprolol and carvedilol treated patients, respectively, had stopped treatment at discharge. None of.the f.gures dif.ered signif.cantly between the two treatment groups and no baseline parameter predicted BB tolerability. Thus, almost twice the number of.unselected patients with systolic CHf.attending a heart f.ilure clinic f.cusing on systematic medical titration were intolerant to BB treatment and only a minority reached target dose treatment. The present data reveal no clear dif.erence with respect to tolerability of.carvedilol and bisoprolol, and no parameter predicts tolerability.

关键词： β受体阻滞剂充血性心力衰竭耐受情况比索洛尔收缩性目标量平均剂量日常应用患者数量显著性差别

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Carbonaceous aerosol transport f.om the Indo-Gangetic Plain to the Himalayas:Carbon isotope evidence and light absorption characteristics

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Geoscience f.ontiers 2023年第2期14卷 105-115页

作者： Pengf.i Chen Shichang Kang Chaoliu Li Zhaof. Hu Lekhendra Tripathee Mukesh Rai Tao Pu Xiuf.ng Yin Örjan gustafsson State Key Laboratory of.Cryospheric Science Northwest Institute of Eco-Environment and ResourcesChinese Academy of Sciences(CAS)Lanzhou 730000China University of.Chinese Academy of.Sciences Beijing 100049China Department of.Environmental Science The Bolin Centre for Climate ResearchStockholm UniversityStockholm 10691Sweden The Bolin Centre f.r Climate Research Stockholm UniversityStockholm 10691Sweden

The Indo-Gangetic Plain(IGP)is a major regional and global emitter of.atmospheric pollutants,which adversely af.ect surrounding areas such as the *** present a comprehensive dataset on carbonaceous aerosol(CA)composition,radiocarbon(D14C)-based source apportionment,and light absorption of.total suspended particle(TSP)samples collected over a 3-year period f.om high-altitude Jomsom in the central *** 3-year mean TSP,organic carbon(OC),and elemental carbon(EC)concentrations were 92.0±28.6,9.74±6.31,and 2.02±1.35 lg m^(3),respectively,with the highest concentrations observed during the pre-monsoon season,f.llowed by the post-monsoon,winter,and monsoon *** △^(14)C analysis revealed that the contribution of.f.ssil f.el combustion(f.ossil)to EC was 47.9%±11.5%,which is consistent with observations in urban and remote regions in South Asia and attests that EC likely arrives in Jomsom f.om upwind IGP sources via long-range *** addition,the lowest f.(f.ssil)(38.7%±13.3%)was observed in winter,indicating large contributions in this season f.om local biomass *** mass absorption cross-section of.EC(MACEC:8.27±1.76 m^(2)/g)and watersoluble organic carbon(MACWSOC:0.98±0.45 m^(2)/g)were slightly higher and lower than those reported in urban regions,respectively,indicating that CA undergo an aging *** aerosol coating during transport and variation of.biomass burning probably led to the seasonal variation in MAC of.two ***,WSOC contributed considerably to the light absorption(11.1%±4.23%)of.*** f.ndings suggest that to protect glaciers of.the Himalayas f.om pollution-related melting,it is essential to mitigate emissions f.om the IGP.

关键词： Carbonaceous aerosol Long-range transport Carbon isotope Source apportionment Light absorption The Himalayas

Towards rational use of.drugs in Egypt

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Towards rational use of drugs in Egypt

Prostaglandin E2 receptor EP3 regulates both adipogenesis and lipolysis in mouse white adipose tissue

第十五届国际药理学大会

作者： Khayyal M. A Khayyal M. T Ibrahim M Abdel Khalek E Nassar M Tantawy f.Abdul Sayed Y BrφsenK Bergman U Rane A gustafsson L. Sjoqvist f. f.culty of.Med Azhar f.culty of.Med f.culty of.Pharmacy Cairo University f.culty of.Med Menof.a f.culty of.Med Shebin-El-Kom Teaching Hosp Helal Hlth.Insurance Hosp. f.culty of.Med Shebin-El-Kom Teaching Hosp. f.culty of.Med Shebin-El-Kom Teaching Hosp. Clin.Pharmacology Dept University of South Denmark Sweden. Clin.Pharmacology Dept Karolmska Inst. Sweden. Clin.Pharmacology Dept Karolmska Inst. Sweden. Clin.Pharmacology Dept Karolmska Inst. Sweden. Clin.Pharmacology Dept Karolmska Inst. Sweden.

＜正＞ A collaborative project between Egypt. Denmark and Sweden has been initiated to improve drug utilization in Egyptian hospitals （Tempus grant JEP - 31033）. Drug and therapeutics committees （DTCs） were f.unded f.om clinicians supported by pharmacological and pharmaceutical expertise. Data collected retrospectively led to identif. the most commonly used drugs and their irrational use. Through consultations at the initial phase （1 year）, drug utilization of.some commonly prescribed drugs f.ll by about 40 % . Emphasis has been put on the principles of.drug evaluation in the training of.DTC members. Preliminary results suggest that it is possible f.r DTCs to change drug utilization towards a more rational approach.

关键词： Drag rationalization Egyptian trial Tempus

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Journal of.Molecular Cell Biology 2016年第6期8卷 518-529页

作者： Hu Xu Jia-Lin f. Yi-f.i Miao Chun-Jiong Wang Qi-f.i Han Sha Li Shi-Zheng Huang Sheng-Nan Du Yu-Xiang Qiu Ji-Chun Yang Jan-Ake gustafsson Richard MBreyer f.ng Zheng Nan-Ping Wang Xiao-Yan Zhang You-f.i Guan Department of.Physiology and Pathophysiology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Center f.r Nuclear Receptors and Cell Signaling Department of Biology and BiochemistryUniversity of HoustonHoustonTX 77204USA Department of.Veterans Af.airs Tennessee Valley Health Authorityand Department of MedicineVanderbilt University Medical CenterNashvilleTN 37232USA Advanced Institute f.r Medical Sciences Dalian Medical UniversityDalian 116044China Department of.Physiology AstraZeneca–Shenzhen University Joint Institute of NephrologyShenzhen University Health Science CenterShenzhen 518060China

Among the f.ur prostaglandin E2 receptors,EP3 receptor is the one most abundantly expressed in white adipose tissue(WAT).The mouse EP3 gene gives rise to three isof.rms,namely EP3α,EP3β,and EP3γ,which dif.er only at their C-terminal *** date,f.nctions of.EP3 receptor and its isof.rms in WAT remain incompletely *** this study,we f.und that the expression of.all EP3 isof.rms were downregulated in WAT of.both db/db and high-f.t diet-induced obese *** ablation of.three EP3 receptor isof.rms(EP3^(−/−)mice)or EP3αand EP3γisof.rms with EP3βintact(EP3βmice)led to an obese phenotype with increased f.od intake,decreased motor activity,reduced insulin sensitivity,and elevated serum *** the dif.erentiation of.preadipocytes and mouse embryonic f.broblasts to adipocytes was markedly f.cilitated by either pharmacological blockade or genetic deletion/inhibition of.EP3 receptor via the cAMP/PKA/PPARγpathway,increased adipogenesis may contribute to obesity in EP3^(−/−)and EP3β***,both EP3^(−/−)and EP3βmice had increased lipolysis in WAT mainly due to the activated cAMP/PKA/hormone-sensitive lipase *** together,our f.ndings suggest that EP3 receptor and itsαandγisof.rms are involved in both adipogenesis and lipolysis and inf.uence f.od intake,serum lipid levels,and insulin sensitivity.

关键词： arachidonic acid EP3 receptor isof.rm PKA PPARγ insulin resistance obesity

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非抗生素药物在大家畜子宫病治疗上的应用

动物医学进展 1987年第1期 20-22页

作者： B、K、gustafsson 刘智喜

刚分娩后,当循环中高水平雌激素使子宫致敏时,催产素的子宫收缩作用即增强。当在6—10小时期间静脉滴注催产素或每日肌注催产素3—4次,连续2—3天时,催产素的效果最佳。当把麦角新碱用于产犊后的母牛时,总是无益的。在产后头10天,一次... 详细信息

刚分娩后,当循环中高水平雌激素使子宫致敏时,催产素的子宫收缩作用即增强。当在6—10小时期间静脉滴注催产素或每日肌注催产素3—4次,连续2—3天时,催产素的效果最佳。当把麦角新碱用于产犊后的母牛时,总是无益的。在产后头10天,一次或多次注射前列腺素f.a(PGf.a),可加速子宫的复旧。单用雌激素类也足以满足对产后轻度至中度子宫感染治疗的需要。对各种消毒剂的宫内灌注是不提倡的。促性腺素释放激素（GnRH）可提高胎衣不下病牛的繁殖力。PGf.a1—2次注射,对具有发情周期母牛的轻度至中度子宫内膜炎是有益的。碘溶液宫内灌注也可以诱发发情。该疗法可替代PGf.a满意地用于轻度至中度子宫内膜炎病例的治疗。几乎没有一种疾病比大家畜子宫感染的疗法多。局部最常应用的抗生素,已普遍作为选择疗法。虽然最初对其疗效主要凭经验判定,而一些对照研究还是探讨了许多疗法的疗效。随着人们对细菌耐药性和组织残留危险的认识,生产肉、乳时,必须有停药时间,必需以非抗生素药物来代替,已日益清楚。本文讨论了有关子宫感染非抗菌疗法的某些重要特征。

关键词：子宫内膜炎疗法胎衣不下胎盘滞留子宫感染母牛雌激素类子宫弛缓发情周期抗生素药物

双异丙吡胺及去烃代谢物的药代学和药效学研究

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中国新药与临床杂志 1983年第4期 6-9页

作者：江文德,Bahr CV,Dahlqvist R,Magnusson A,Sjqvist f.Calissendorf.B,Emilsson H,Schenck-gustafsson K,Vuorisalo D 上海第一医学院药理学教研室瑞典卡洛琳斯卡医学院临床药理学教研室瑞典卡洛琳斯卡医学院临床药理学教研室瑞典卡洛琳斯卡医学院临床药理学教研室瑞典卡洛琳斯卡医学院临床药理学教研室 Huddinge大学医院眼科 Huddinge大学医院药剂科 Huddinge大学医院内科 Huddinge大学医院内科

双异丙吡胺(disopyramide,下简称D)约有45％可在肝内代谢,其主要代谢产物为N-去烃化合物(MND),后者的血药浓度约为母体的10-20％,也可有20倍的个体差异。肾病患者长期用药时MND的血药浓度将特别高。离体豚鼠回肠及心房的实验证明,MND的... 详细信息

双异丙吡胺(disopyramide,下简称D)约有45％可在肝内代谢,其主要代谢产物为N-去烃化合物(MND),后者的血药浓度约为母体的10-20％,也可有20倍的个体差异。肾病患者长期用药时MND的血药浓度将特别高。离体豚鼠回肠及心房的实验证明,MND的抗胆硷效价为D的20倍,而延长心房不应期的效价仅为D的1/4。到目前为止,尚无MND用于人体的作用和药代参数的报告。本文系欧洲人静注D及MND的药代动力学及其药效学的首次研究报告。

关键词：静注药代动力学药代学药物动力学血药浓度双异丙吡胺 MND 代谢产物代谢物

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