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中国临床康复 2006年第11期10卷 107-110页

作者：黄敬群罗晓星王四旺谢艳华解放军第四军医大学药学系药物研究所陕西省西安市710032 解放军第四军医大学药学系药理学教研室陕西省西安市710032

目的:观察传统中药肉桂挥发油中桂皮醛的细胞毒作用,并以小鼠S180移植性肿瘤为模型,进行其体内外抗肿瘤活性及对S180荷瘤小鼠免疫功能影响的实验。方法:实验于2005-03/06在解放军第四军医大学药学系药物研究所实验室完成。取BALB/c小鼠6... 详细信息

目的:观察传统中药肉桂挥发油中桂皮醛的细胞毒作用,并以小鼠S180移植性肿瘤为模型,进行其体内外抗肿瘤活性及对S180荷瘤小鼠免疫功能影响的实验。方法:实验于2005-03/06在解放军第四军医大学药学系药物研究所实验室完成。取BALB/c小鼠60只,雌雄各半,体质量18～22g。先设1组不接种瘤株的生理盐水正常对照组,10只,雌雄各半。余50只小鼠每只右腋皮下接种0.2mL,24h后随机分成5组,即生理盐水荷瘤对照组,卡铂阳性药对照组,桂皮醛25,50,100mg/kg3个剂量组,每组10只,雌雄各半。用四甲基偶氮唑蓝法观察桂皮醛对6种人癌细胞的体外抗肿瘤作用;对25,50,100mg/kg3个剂量组分别腹腔注射相应剂量用含0.5%土温80生理盐水溶解的桂皮醛(购自中国医药集团上海化学试剂公司),正常对照组和荷瘤空白对照组腹腔注射生理盐水,阳性药对照组腹腔注射卡铂5mg/kg。接种第2天开始全部腹腔注射给药,10mL/kg,每天1次,连续给药10d,于最后1次给药后次日处死动物,测定肿瘤抑制率、免疫器官质量、血常规、NK细胞活性、T淋巴细胞转化率,分析其对小鼠体内抗肿瘤作用及与免疫调节的关系。结果:参加实验的动物60只全部进入结果分析,没有脱失。①桂皮醛对体外培养的6种人肿瘤细胞有直接细胞毒作用,其IC50的范围为12.3～37.1mg/L。②桂皮醛50,100mg/kg剂量组对S180荷瘤小鼠肿瘤生长有明显抑制作用,抑瘤率分别为33.08%和46.92%;同时能有效保护荷瘤小鼠胸腺和脾脏指数。③桂皮醛25,50mg/kg剂量组可以升高白细胞,与生理盐水荷瘤对照组比差异有显著性意义(11.13±1.49,11.25±2.18,8.78±1.33,P<0.01)。④桂皮醛25,50mg/kg剂量组的T淋巴细胞增殖能力显著或非常显著高于生理盐水荷瘤对照组(P<0.05～0.01);桂皮醛50mg/kg剂量组NK细胞杀伤活性明显高于生理盐水荷瘤对照组(P<0.05)。⑤桂皮醛100mg/kg剂量组显著降低白细胞(P<0.01);抑制T淋巴细胞增殖能力和NK细胞杀伤活性,与荷瘤空白对照组比较差异有显著性意义(P<0.01)。结论:桂皮醛对体外培养的肿瘤细胞增殖具有良好的抑制作用,在适当剂量范围内可以保护和恢复荷瘤小鼠的免疫功能。

关键词：抗肿瘤药植物提取物/药理学肉桂/化学抗肿瘤药/投药和剂量免疫细胞/药物作用

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天灸对肺癌小鼠骨髓有核细胞和外周白细胞的影响及其抗肿瘤作用

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中国临床康复 2006年第11期10卷 132-134页

作者：王颖李学武赵立岩李南玲国家广播电影电视总局门诊部经络治疗室北京市100866 北京中医药大学针灸学院北京市100029

目的:观察天灸籍药物穴位敷贴及药物本身的治疗作用对顺铂化疗Lewis肺癌小鼠骨髓有核细胞的影响,以及肿瘤生长的抑制。方法:实验于2005-02在北京中医药大学针灸学院针灸机理实验室进行。将40只C57BL/6J近交系小鼠随机分为4组:正常组、... 详细信息

目的:观察天灸籍药物穴位敷贴及药物本身的治疗作用对顺铂化疗Lewis肺癌小鼠骨髓有核细胞的影响,以及肿瘤生长的抑制。方法:实验于2005-02在北京中医药大学针灸学院针灸机理实验室进行。将40只C57BL/6J近交系小鼠随机分为4组:正常组、模型组、化疗组、天灸+化疗组,各10只。正常组:不做肺癌移植肿瘤模型造模,不处理;模型组:只造模,不处理;化疗组:造模4d后,腹腔注射顺铂,0.2mL/只,含顺铂0.05mg,连用5d。天灸+化疗组:在造模化疗的同时,贴天灸膏(药物组成为麝香、淫羊藿、三七、黄芪、辣椒,按1∶20∶20∶20∶40比例调配),8h/次,1次/d,共治疗11次。天灸治疗结束后次日,即第14d统一处死取材。观察天灸后各组小鼠净体质量变化、瘤质量、抑瘤率,以及天灸对化疗小鼠骨髓有核细胞、外周血白细胞的影响。结果:40只小鼠均进入结果分析。①化疗组和天灸+化疗组净体质量与模型组相比,明显降低,而天灸有减轻小鼠体质量下降的趋势[(15.03±0.63),(15.75±0.40),(21.57±0.56)g;t=8.35,6.78,P<0.001]。②化疗组和天灸+化疗组瘤质量与模型组相比,均明显降低,但天灸+化疗组减轻的程度较大[(2.35±0.27),(2.2±0.13),(3.44±0.28)g;t=3.56,4.65,P<0.01];在抑瘤率方面,天灸+化疗组亦比化疗组高(36.0%,31.7%)。③天灸+化疗组外周白细胞数目与模型组相比明显上升[(8.32±0.55),(10.88±0.84)×109L-1,t=2.76,P<0.05],而化疗组外周白细胞数目较正常组明显下降[(7.38±0.56),(9.85±0.93)×109L-1,t=2.51,P<0.05],且天灸+化疗组与化疗组之间有显著性差异(t=3.86,P<0.01)。④化疗组骨髓有核细胞数目与模型组相比明显减少[(3.36±0.72)×106L-1,(1.77±0.33)×106L-1,t=2.96,P<0.05],而天灸+化疗组的骨髓有核细胞数目,比化疗组明显升高[(3.37±0.48)×106L-1,t=2.43,P<0.05]。结论:天灸膏有增强化疗抗肿瘤的作用,减轻化疗的毒副作用。这种辅助治疗效果可能与显著提高化疗处理中肺癌模型小鼠骨髓有核细胞数目,以及提高化疗过程中肺癌小鼠血液白细胞数目有关。

关键词：穴输(五输) 发泡疗法肿瘤/并发症肿瘤/药物疗法免疫细胞/药物作用白细胞减少/化学诱导

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IMMUNOENHANCING EFFECTS OF ALPRAZOLAM, A BENZODIAZEPINE RECEPTOR AGONIST

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1992年第1期650卷 132-139页

作者： FRIDE, E MENG, R SKOLNICK, P ARORA, PK NIDDK NEUROSCI LAB ROOM 111 BLDG 8 BETHESDA MD 20892 USA

The effects of alprazolam (ALP), a triazolobenzodiazepine with high affinity for 'central' benzodiazepine receptors, were examined on several parameters of immune function in mice. NK, MLR, and mitogen-induced lymphocyte proliferation were all significantly increased 2 hr after administration of low doses (0.02-1.0 mg/kg) of ALP. Twenty four hr later, similar but less robust immunoenhancing effects were observed. These measures of immune functions were not affected by higher doses of ALP (5-10 mg/kg). The immunoenhancing effects of ALP did not appear related to serum corticosterone levels. These and other findings demonstrate that the GABA/benzodiazepine receptor chloride channel complex can bidirectionally modulate immune function.

关键词：阿普唑仑/投药和剂量细胞毒性免疫/药物作用剂量效应关系药物免疫/药物作用免疫细胞/药物作用杀伤细胞天然/免疫学淋巴细胞活化/药物作用受体 GABA-A/药物作用时间因素动物男(雄)性小鼠

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CELL-MEDIATED-IMMUNITY - ITS MODULATION BY DIMETHYL-SULFOXIDE

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1975年第JAN27期243卷 81-90页

作者： BARTFELD, H GOLDSTEIN, A ST VINCENTS HOSP & MED CTR DEPT MED IMMUNOL & CONNECTIVE TISSUE DIV NEW YORK NY 10011 USA

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Immunomodulation by fungal toxins

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JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS 2000年第2期3卷 109-143页

作者： Bondy, GS Pestka, JJ Hlth Canada Food Directorate Toxicol Res Div Hlth Protect Branch Ottawa ON K1A 0L2 Canada Michigan State Univ Dept Food Sci & Human Nutr E Lansing MI 48824 USA Michigan State Univ Dept Microbiol E Lansing MI 48824 USA Michigan State Univ Natl Ctr Food Safety & Toxicol E Lansing MI 48824 USA

The availability of immunotoxicity data for fungal toxins varies considerably for different toxins. The following is a comprehensive review of the most recent literature on the immunotoxicity of aflatoxins, fumonisins, gliotoxin, ochratoxins, patulin, and trichothecenes. Aflatoxin is an immunomodulating agent that acts primarily on cell-mediated immunity and phagocytic cell function. in addition to further characterization of aflatoxin-induced immunotoxicity in various species, some recent studies have focused on ameliorating the effects of aflatoxin by supplementing or amending the diet. The immunomodulatory effects of ochratoxins have also been considered for many years. Notably, recent studies have examined immune function in the offspring of rats and mice exposed to ochratoxin pre- and perinatally. Fumonisin toxicity has been characterized relatively recently in comparison to aflatoxin and ochratoxin, and fumonisin-induced immonotoxicity is an area of active research. As these studies progress, they may also clarify the role of sphingolipid metabolism in immune function. The most recent study of patulin immunotoxicity in mice indicates that exposure to levels found in foods and feeds would not likely result in immunotoxicity. Exposure to gliotoxin would most likely be by infection with gliotoxin-producing fungi. Although the toxin is immunosuppressive in vitro, the link between immunosuppression and the presence of gliotoxin in infected tissues in vivo has yet to be made. The trichothecenes can both suppress and stimulate immune function. By comparison, more information is available on the molecular events associated with trichothecene-induced immunomodulation than for any other fungal toxins. The molecular basis of immune function modulation by fungal toxins remains a frontier for future research.

关键词：环境暴露食品污染免疫细胞/药物作用免疫抑制法免疫毒素类/免疫学免疫毒素类/药理学真菌毒素类/免疫学真菌毒素类/药理学吞噬作用/生理学鞘脂类/代谢猪动物小鼠兔大鼠

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In vivo cytokine production and resistance to infection after acute exposure to 3,4-dichloropropionaniline

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JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A 2000年第6期60卷 391-406页

作者： Watson, VA Barnett, JB Schafer, R W Virginia Univ Robert C Byrd Hlth Sci Ctr Sch Med Dept Microbiol & Immunol Morgantown WV 26506 USA

3,4-Dichloropropionaniline (propanil) is an extensively used postemergent herbicide that has been shown to produce toxic and immunotoxic effects. The present report examined if acute exposure to propanil altered in vitro or in vivo cytokine production in response to antigenic stimulation. Studies to determine resistance to infection by the intracellular bacterium Listeria monocytogenes after exposure to propanil Were also conducted. Our experiments demonstrate that in vivo exposure to propanil during bacterial infection reduced the subsequent in vitro production of interferon-gamma (IFN-gamma) by splenocytes and liver nonparenchymal cells in response to antigenic and mitogenic stimulation. Additional experiments examined the production of cytokines in vivo after propanil exposure alone or combined propanil exposure and L. monocytogenes infection. It was found that the endogenous levels of cytokines in the liver, spleen, and blood were similar in control and propanil-treated mice. The levels of cytokines Were also similar in control and exposed mice that were infected With L. monocytogenes. Initial resistance to the infection was not affected by exposure to propanil. These results demonstrate that in vivo exposure to propanil during a bacterial infection suppresses the subsequent in vitro production of cytokines but that the endogenous levels are not affected during the initial stages of infection.

关键词：细胞培养的离心法梯密度胆酸类/化学细胞因子类/生物合成细胞因子类/血液酶联免疫吸附测定除莠剂/毒性免疫细胞/药物作用干扰素Ⅱ型/生物合成干扰素Ⅱ型/血液白细胞介素1/生物合成白细胞介素1/血液白细胞介素6/生物合成白细胞介素6/血液利斯特菌感染/免疫学肝/药物作用肝/免疫学肝/微生物学小鼠近交C57BL 敌稗/毒性无特异性病原体有机物脾/药物作用脾/免疫学脾/微生物学肿瘤坏死因子α/分析肿瘤坏死因子α/生物合成动物女(雌)性小鼠

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PROPERTIES OF PRIMED SUPPRESSOR T-CELLS AND THEIR PRODUCTS

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TRANSPLANTATION REVIEWS 1975年第1期26卷 106-129页

作者： TADA, T TANIGUCHI, M TAKEMORI, T CHIBA UNIV SCH MEDLABS IMMUNOLCHIBAJAPAN

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EVALUATION OF THE GROWTH-RATE OF MCF-7 BREAST-CANCER MULTICELLULAR SPHEROIDS USING 3 MATHEMATICAL-MODELS

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CELL PROLIFERATION 1994年第4期27卷 213-223页

作者： OLEA, N VILLALOBOS, M NUNEZ, MI ELVIRA, J DEALMODOVAR, JMR PEDRAZA, V DepartmentofRadiology SchoolofMedicineUniversityofGranadaSpain.

Growth data on 60 multicellular spheroids of MCF-7 human breast cancer cells were fitted, on an individual basis, by the Gompertz, Bertalanffy and logistic equations. MCF-7 spheroids, initiated and grown in medium containing oestrogens, exhibited a growth rate that decreased continuously as spheroid size increased. Plots of spheroid volume v. time generated sigmoid curves that showed an early portion with an approximately exponential volume increase;a middle region or retardation phase characterized by a continuously decreasing growth rate;and, finally, a late segment or plateau phase approaching zero growth rate, that permitted an estimate of the maximum spheroid size (V(max)). Growth curves generated by MCF-7 spheroids under different experimental conditions (hormones, drugs and radiation exposures) can be compared after normalization. Linearized forms of the fitted Gompertz curves provided a convenient way to express differences in growth rate.

关键词：乳腺肿瘤/病理学癌/病理学细胞分裂/药物作用培养基雌激素类/投药和剂量雌激素类/药理学模型生物学球形体细胞/药物作用球形体细胞/病理学女(雌)性人类

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Photodynamic therapy of human glioma spheroids using 5-aminolevulinic acid

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PHOTOCHEMISTRY AND PHOTOBIOLOGY 2000年第1期72卷 128-134页

作者： Madsen, SJ Sun, CH Tromberg, BJ Wallace, VP Hirschberg, H Univ Nevada Dept Hlth Phys Las Vegas NV 89154 USA Univ Nevada Las Vegas Canc Inst Las Vegas NV 89154 USA Univ Calif Irvine Beckman Laser Inst & Med Clin Irvine CA 92715 USA Univ Oslo Rikshosp Dept Neurosurg N-0027 Oslo Norway

The response of human glioma spheroids to 5-aminole-vulinic acid (ALA)-mediated photodynamic therapy (PDT) is investigated. A two-photon fluorescence microscopy technique is used to show that human glioma cells readily convert ALA to protoporphyrin IX throughout the entire spheroid volume. The central finding of this study is that the response of human glioma spheroids to ALA-mediated PDT depends not only on the total fluence, but also on the rate at which the fluence is delivered. At low fluences (less than or equal to 50 J cm(-2)), lower fluence rates are more effective. At a fluence of 50 J cm(-2), near-total spheroid kill is observed at fluence rates of as low as 10 mW cm(-2). The fluence rate effect is not as pronounced at higher fluences (>50 J cm(-2)), where a favorable response is observed throughout the range of fluence rates investigated, The clinical implications of these findings are discussed.

关键词：氨基酮戊酸/药代动力学氨基酮戊酸/药理学胶质母细胞瘤/药物疗法胶质母细胞瘤/代谢显微镜检查荧光光化学疗法原卟啉类/代谢球形体细胞/药物作用球形体细胞/代谢人类

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IMMUNOADJUVANT ACTIVITY OF PYRAN COPOLYMER .1. EVIDENCE FOR DIRECT STIMULATION OF T-LYMPHOCYTES AND MACROPHAGES

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CELLULAR IMMUNOLOGY 1975年第2期20卷 167-176页

作者： BAIRD, LG KAPLAN, AM VIRGINIA COMM UNIV CANC CTRMED COLLDIV MED ONCOLRICHMONDVA 23298 VIRGINIA COMM UNIV MED COLLDEPT SURGPOB 756RICHMONDVA 23298 VIRGINIA COMM UNIV MED COLLDEPT MICROBIOLRICHMONDVA 23298

A single injection of pyran copolymer has been shown to greatly increase the number of hemolytic plaque forming cells to sheep erythrocytes (sRBC). Pyran given from 1 day before to 2 days after sRBC inoculation increased both specific activity and plaques/spleen, suggesting that macrophage activation was probably not responsible for the enhancement seen. In addition, pyran given 1 day prior to the primary injection of sRBC was found to increase the secondary response to SRBC given alone. As similar experiments using thymectomized irradiated bone marrow reconstituted mice showed no increase in specific activity following pyran administration, it was unlikely that pyran was acting directly on B cells. Furthermore, experiments measuring the antibody response to Escherichia coli lipopolysaccharide, a thymic independent antigen, pyran did not increase the response to this antigen. In contrast to the above, pyran delayed and depressed cell mediated cytotoxicity to the allogeneic DBA/2 P815 mastocytoma. However, no difference in the titers of cytotoxic antibody against mastocytoma cells was seen between pyran-treated and normal animals. Pyran was mitogenic for spleen cells in vitro . However, following the administration of pyran in vivo , mitogen induced blastogenesis in vitro to PHA and LPS was inhibited and this inhibition was determined to be macrophage-dependent. These results are consistent with a model in which the immunoregulatory effects of pyran act through macrophages and T-lymphocytes.

关键词：佐剂免疫抗体生成/药物作用溶血性斑块技术免疫细胞/药物作用免疫接种加强淋巴细胞活化/药物作用巨噬细胞/免疫学小鼠近交C57BL 小鼠近交DBA 聚合物/药理学吡喃共聚物/药理学脾/免疫学 T淋巴细胞/免疫学时间因素动物小鼠

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