重组别藻蓝蛋(rAPC)抑瘤活性及其对免疫作用的研究

目的:观察重组别藻蓝蛋白(rAPC)对接种H22肝癌细胞小鼠的抑瘤活性及其免疫作用.方法:昆明小鼠随机分为5组(10只/组),即模型组、rAPC低、中、高剂量组(25,50,100mg/kg·d)、环磷酰胺组(CY对照组).建立小鼠肝癌1422移植瘤模型,次日除模型组外,其余4组分别以不同剂量的rAPe、CY灌胃,于15d后处死,完整剥离出肿瘤、胸腺、脾脏,准确称重,计算抑瘤率、胸腺指数和脾指数,并采用放免法(PIA)测定血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的水平.结果:rAPC低剂量组小鼠H22肿瘤质量增长较模型组缓慢(P＜0.05),中、高剂量组较模型组显著缓慢(P＜0.01),抑瘤率分别为25.2%、36.7%、43.1%;rAPC各剂量组能升高胸腺指数、脾指数和血清中细胞因子IL-6、TNF-α的水平.结论:rAPC可有效抑制H22肝癌的生长,促进小鼠胸腺和脾脏的生长发育,提高小鼠的免疫功能,从而抑制肿瘤的生长.     

重组别藻蓝蛋白(rAPC)抑瘤活性及其对免疫作用的研究(英文)

目的:观察重组别藻蓝蛋白(rAPC)对接种H22肝癌细胞小鼠的抑瘤活性及其免疫作用。方法:昆明小鼠随机分为5组(10只/组),即模型组、rAPC低、中、高剂量组(25,50,100mg/kg·d)、环磷酰胺组(CY对照组)。建立小鼠肝癌H22移植瘤模型,次日除模型组外,其余4组分别以不同剂量的rAPC、CY灌胃,于15d后处死,完整剥离出肿瘤、胸腺、脾脏,准确称重,计算抑瘤率、胸腺指数和脾指数,并采用放免法(RIA)测定血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的水平。结果:rAPC低剂量组小鼠H22肿瘤质量增长较模型组缓慢(P<0.05),中、高剂量组较模型组显著缓慢(P<0.01),抑瘤率分别为25.2%、36.7%、43.1%;rAPC各剂量组能升高胸腺指数、脾指数和血清中细胞因子IL-6、TNF-α的水平。结论:rAPC可有效抑制H22肝癌的生长,促进小鼠胸腺和脾脏的生长发育,提高小鼠的免疫功能,从而抑制肿瘤的生长。     

不同剂量朱砂七总蒽醌对H22荷瘤小鼠免疫功能及抗氧化能力的影响

目的:探讨不同剂量朱砂七总蒽醌对H22荷瘤小鼠免疫功能及抗氧化能力的影响。方法:选取清洁级昆明小鼠60只,按照随机数字表法分为正常对照组、H22荷瘤组、环磷酰胺组、低剂量组、中剂量组、高剂量组,每组各10只。除正常对照组外,其余5组小鼠建立H22荷瘤小鼠模型。低剂量组、中剂量组、高剂量组分别给予0.3 g/kg、0.6 g/kg、1.2 g/kg的朱砂七总蒽醌悬浊液干预,环磷酰胺组给予0.02 g/kg的环磷酰胺干预,正常对照组和H22荷瘤组给予等剂量的1%的羧甲基纤维素钠干预。比较各组小鼠的肿瘤体质量、抑瘤率、T淋巴细胞亚群以及血清超氧化歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、乳酸脱氢酶(LDH)水平。结果:环磷酰胺组、高剂量组的肿瘤体质量低于低剂量组,抑瘤率高于低剂量组,差异具有统计学意义(P0.05)。高剂量组的CD4+、CD4+/CD8+均高于环磷酰胺组、低剂量组、中剂量组,CD8+低于环磷酰胺组、低剂量组、中剂量组,差异均有统计学意义(P0.05)。高剂量组血清SOD、GSH-Px水平高于其他5组,MDA、LDH水平低于H22荷瘤组、低剂量组、中剂量组,差异均有统计学意义(P0.05)。结论:朱砂七总蒽醌具有明显的抗肿瘤作用,可增强小鼠的免疫功能和抗氧化能力,且具有剂量效应。     

产毒金黄色葡萄球菌鉴定及在百叶中生长与产毒特性分析

从生鲜食品中分离鉴定得到产肠毒素SEA的金黄色葡萄球菌（Staphyloccocus aureus）菌株,研究金黄色葡萄球菌在百叶中的生长变化及产肠毒素特性。将不同浓度的金黄色葡萄球菌同时接种到减菌（样品组）和未减菌（对照组）百叶中,高、低初始接种量分别控制在4.0 lg(cfu/g)和2.0 lg(cfu/g)左右,并定时追踪不同储存温度条件下百叶中金黄色葡萄球菌的活菌数及产毒情况。金黄色葡萄球菌肠毒素的检测采用商业化的ELISA试剂盒。在37 ℃储存过程中,金黄色葡萄球菌在样品组中不但能生长良好并在18 h后菌落数可达到7.0 lg(cfu/g)并被检测出肠毒素,对照组中金黄色葡萄球菌生长良好菌落数可达到7.0 lg(cfu/g)却未检测出产肠毒素。在25、15和5 ℃储存过程中,样品组和对照组百叶都未检测出肠毒素。温度对金黄色葡萄球菌在百叶中是否产肠毒素具有决定性的作用,且百叶中本身存在的杂菌可能可以抑制金黄色葡萄球菌产肠毒素。     

凹顶藻萜类化合物对小鼠H22肿瘤生长及VEGF、PCNA表达的影响

目的:观察凹项藻提取物(Laurenciaterpenoid extract,LET)对接种H22细胞小鼠的肿瘤生长及血管内皮细胞生长因子(VEGF)、增殖细胞核抗原(PCNA)表达的影响.方法:昆明小鼠随机分为5组(10只,组),即模型组、LET低中高剂量组(25、50、100 mg/kg·d-1)、环磷酰胺组(CTX对照组).各组小鼠左前腋下皮下接种H22肝癌细胞,第二天除模型组外,其余4组分别以不同剂量的LET、CTX灌胃,于15天后处死,完整剥离出肿瘤,称重,计算抑瘤率.免疫组化法测定肿瘤组织中VEGF、PCNA的表达.结果:LET低、中、高剂量组小鼠H22肿瘤质量增长均较模型组缓慢(P<0.05),抑瘤率分别为27.5%、34.9%、41.4%;同时LET中、高剂量组VEGF阳性表达较模型组显著减少(P<0.05),低剂量组未见明显变化,但LET各剂量组PCNA阳性表达较模型组显著减少(P<0.05).结论:LET各剂量组可以抑制小鼠H22肿瘤的生长,具有较高的抑瘤活性,且中、高剂量组能抑制VEGF的表达(P<0.05),低、中、高剂量组能抑制PCNA的表达(P<0.05).LET对肿瘤组织VEGF、PCNA表达的抑制作用可能是其抗H22肿瘤及抗血管生成的一个重要原因.     

Antitumor effect of staphylococcal enterotoxin A on mice

以实验室建立的S180小鼠肿瘤模型为研究对象,采用腹腔注射给药,观察葡萄球菌肠毒素A(SEA)在体内抑制肿瘤的效果.实验表明,SEA抑肿瘤率为40.18％,显示对肿瘤有一定的抑制作用;能显著刺激脾脏细胞增殖,使脾指数升高至11.3mg/g;使血清和脾组织中IL-2水平分别升至69.77 pg/mL和682.43pg/mL;且能诱导肿瘤组织中产生大量的CD4+T细胞和CD8+T细胞.结果显示,SEA在机体内对免疫功能有正向调节作用,从而在一定程度上抑制了肿瘤细胞的生长.     

肺炎克雷伯菌表面成分对小鼠细菌感染的保护作用

观察肺炎克雷伯菌 (Klebsiellapneumoniae,Kp)表面成分在小鼠体内对细菌感染的保护作用。经肺炎克雷伯菌培养液经溶菌酶、NP40溶菌后 ,再经去脂、去蛋白和有机溶剂沉淀 ,干燥获取Kp表面成分干粉。用不同剂量的Kp表面成分免疫小鼠 ,分别用大肠埃希菌和金黄色葡萄球菌攻击小鼠 ,记录小鼠死亡情况 ,并测定循环抗体效价。结果 :Kp表面成分低剂量组 (30 μg/g体重 )和高剂量组 (40 μg/g体重 )对大肠埃希菌和金黄色葡萄球菌感染有显著保护作用 ,能降低感染小鼠的死亡率。免疫后小鼠的抗体效价明显高于对照组小鼠 (P <0 0 1 )。应用Kp表面成分的小鼠对细菌感染有一定的保护作用。     

肺炎克雷伯菌表面成分对小鼠细菌感染的保护作用*

观察肺炎克雷伯菌 (Klebsiellapneumoniae,Kp)表面成分在小鼠体内对细菌感染的保护作用。经肺炎克雷伯菌培养液经溶菌酶、NP40溶菌后 ,再经去脂、去蛋白和有机溶剂沉淀 ,干燥获取Kp表面成分干粉。用不同剂量的Kp表面成分免疫小鼠 ,分别用大肠埃希菌和金黄色葡萄球菌攻击小鼠 ,记录小鼠死亡情况 ,并测定循环抗体效价。结果 :Kp表面成分低剂量组 (30 μg/g体重 )和高剂量组 (40 μg/g体重 )对大肠埃希菌和金黄色葡萄球菌感染有显著保护作用 ,能降低感染小鼠的死亡     

藻蓝蛋白的抑瘤活性及抗氧化作用的研究

目的:观察藻蓝蛋白(phycocyanin,PC)对接种S180肉瘤小鼠的肿瘤生长及抗氧化功能的影响。方法:昆明小鼠随机分为6组(10只/组)。即模型组、PC低、中、高、最高剂量组(25,50,100,200mg/kg·d)、环磷酰胺组(CY对照组)。各组小鼠右前腋窝皮下接种S180肉瘤细胞,第二天除模型组外,其余5组分别以不同剂量的PC灌胃、CY(40mg/kg·d)腹腔注射,15天后处死,完整剥离出肿瘤,称重,计算抑瘤率;测定血浆中SOD活力、MDA含量及红细胞溶血度。结果:1.除PC低剂量组外,中、高、最高剂量组肿瘤生长比模型组显著缓慢(P<0.01),抑瘤率分别为34.8%、56.9%、68.4%、61.9%。2.PC高、最高剂量组可升高小鼠血浆中SOD酶的活力(P<0.05);PC各剂量组均能降低小鼠血浆中MDA的含量,最高剂量组与模型组比较有统计学意义(P<0.05),PC低、中、高剂量组与模型组比较有显著差异(P<0.01)。3.除PC低剂量组外,中、高、最高剂量组均能降低红细胞溶血度(P<0.05),其中高剂量组与模型组比较有显著差异(P<0.01)。结论:PC各剂量组可以抑制小鼠S180肿瘤...     

硬枝树花中抑制H_22荷瘤小鼠肿瘤的活性成分研究

研究了从硬枝树花中提取得到的4个单体化合物松萝酸(usnic acid)、去甲环萝酸(evernic acid)、巴尔巴地衣酸(barbatic acid)和水杨嗪酸(salazinic acid)对H22荷瘤小鼠的抑瘤作用,并且对抑瘤率、胸腺指数、脾指数及小鼠白介素-2含量等各个指标的进行检测,以说明此4种化合物对小鼠肿瘤生长的抑制效果。结果表明,松萝酸高、中剂量组,去甲环萝酸高、中剂量组,巴尔巴地衣酸低剂量组,水杨嗪酸高剂量组对小鼠肿瘤有较好的抑制效果,与阴性对照组比较有极显著差异(P0.01),并且这些组的H22荷瘤小鼠血清中白介素-2的含量显著增加,与抑制肿瘤活性具有相关性。     

金黄色葡萄球菌肠毒素A(SEA)对小鼠体内肉瘤抑制效果

以实验室建立的$180小鼠肿瘤模型为研究对象,采用腹腔注射给药,观察葡萄球菌肠毒素A（SEA）在体内抑制肿瘤的效果。实验表明,SEA抑肿瘤率为40．18％,显示对肿瘤有一定的抑制作用;能显著刺激脾脏细胞增殖,使脾指数升高至11．3mg/g;使血清和脾组织中IL-2水平分别升至69．77pg/mL和682．43pg/mL;且能诱导肿瘤组织中产生大量的CD4^＋T细胞和CD8^＋T细胞。结果显示,SEA在机体内对免疫功能有正向调节作用,从而在一定程度上抑制了肿瘤细胞的生长。     

黄瓜香联合顺铂治疗小鼠H22肝癌的研究

目的 观察黄瓜香联合顺铂对小鼠H22肝癌移植瘤生长的抑制作用.方法 将40只接种H22肝癌细胞的昆明小鼠随机分为4组,其腹腔分别注射生理盐水(对照组);黄瓜香组;顺铂组;黄瓜香+顺铂组(联合治疗组),观察小鼠的毒副反应及生存质量.实验19 d后,处死全部小鼠,剥离皮下肿瘤,称小鼠肿瘤重量,计算抑瘤率.结果 黄瓜香组的H22肝癌平均瘤重为(1.26 ±0.19)g,明显低于对照组的(1.89 ±0.56)g(P ＜0.01).联合治疗组的平均瘤重为(0.57 ±0.42)g,均明显低于黄瓜香组(P＜0.01)和顺铂组(P＜0.01);其抑瘤率达69.8％,明显高于黄瓜香组(x2=16.9875,P＜0.01)和顺铂组(x2=5.0602,P＜0.05).联合治疗组小鼠的毒副反应明显低于顺铂组,生存质量好于顺铂组;黄瓜香组与联合治疗组都能调节肠道菌群,扶植肠道中有益菌(乳酸杆菌和双歧杆菌)生长,抑制大肠埃希菌生长,与对照组比较差异具有统计学意义(P＜0.01).结论 黄瓜香与顺铂合用对小鼠H22肝癌移植瘤的生长具有协同抑制作用,能降低顺铂毒副反应,提高小鼠的生存质量.     

十全育真汤对H22荷瘤小鼠免疫功能的影响

目的：研究十全育真汤对荷瘤小鼠免疫功能的影响,探讨十全育真汤抗肿瘤的作用机制。方法：SPF级雄性昆明种小鼠30只,制成荷H₂₂小鼠肝癌细胞移植瘤模型,随机分为模型组、阳性对照组及十全育真汤组（n=10）;另选择未接种小鼠10只为正常对照组。正常对照组、模型组每天按10 ml/kg灌胃生理盐水及蒸馏水,阳性对照组、十全育真汤组每天按8 g/kg、18 g/kg灌胃参一药液（80 mg/ml）与十全育真汤剂。连续给药14 d后处死小鼠,测量胸腺、脾脏指数及抑瘤率,检测外周血中白细胞、淋巴细胞含量及T细胞亚群CD3、CD4、CD8细胞百分比,血清中白细胞介素2（IL-2）、肿瘤坏死因子α（TNF-α）及干扰素-β（IFN-β）的含量,淋巴细胞增殖能力及NK细胞杀伤功能。结果：较正常对照组,十全育真汤组小鼠体重明显增加,脾脏指数显著增大（P<0.05）;白细胞、淋巴细胞CD4、CD8、CD3及TNF-α含量明显升高（P<0.05）;IL-2、IFN-β含量显著下降（P<0.05）;淋巴细胞增殖能力、NK细胞杀伤功能明显升高（P<0.05）。与模型组相比,十全育真汤组小鼠胸腺、脾脏指数显著增大（P<0.05）;白细胞、淋巴细胞CD3、CD4、IL-2、IFN-β及TNF-α含量明显升高（P<0.05）,CD8含量则显著降低（P<0.05）;NK细胞杀伤功能及淋巴细胞增殖能力显著增加（P<0.05）。结论：十全育真汤可促进H₂₂荷瘤小鼠免疫器官的生长,增强机体免疫功能,有利于肿瘤机体的恢复。     

Natural immunosurveillance against spontaneous, autochthonous breast cancers revealed and enhanced by blockade of IL-13-mediated negative regulation

Introduction We and others previously observed immunosurveillance against transplantable tumors in mice, and enhancement thereof by blockade of negative regulation by T reg cells or the NKT-IL-13-myeloid cell-TGF-β regulatory circuit. However, it was unknown whether natural immunosurveillance inhibits growth of completely spontaneous autochthonous tumors, and whether it can be improved by inhibition of negative regulation. Materials and methods To examine the existence of T cell-mediated immunosurveillance against spontaneous tumors, BALB-neuT mice were treated with anti-CD4 and/or anti-CD8. A role for IL-13 in the suppression of immunosurveillance was investigated by treating mice with IL-13 inhibitor. Results We show that even spontaneous autochthonous breast carcinomas arising in Her-2/neu transgenic mice appear more quickly when the mice are depleted of T cells, evidence for T-cell mediated immunosurveillance slowing tumor growth. This immunosurveillance could be further enhanced by blockade of IL-13 (but not IL-4) which slowed the appearance of these autologous tumors compared to control antibody-treated mice. Conclusion Thus, even completely spontaneous, autochthonous breast cancers can be controlled in part by natural immunosurveillance, and blockade of negative regulation can improve this control. This work was in part supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.     

The antitumor effect of dinitrosyl iron complexes with glutathione in a murine solid-tumor model

A significant antitumor activity of aqueous solutions of binuclear dinitrosyl iron complexes with glutathione was found when they were injected intravenously in a model of a solid malignant tumor, that is, Lewis carcinoma, in mice. Dinitrosyl iron complexes completely inhibited the tumor growth (by 100%) at doses of 20, 10, and 2 μmol/kg in the first 11 days after the beginning of experiment followed by tumor proliferation at a rate that was lowest for the lowest of the used doses. At day 16, the inhibition of tumor growth was 90% when a solution of dinitrosyl iron complexes was injected at a dose of 2 μmol/kg five times with an interval of 2 to 3 days between injections; whereas the inhibition of tumor growth did not exceed 70 and 30% at doses of 10 and 20 μmol/kg, respectively. Acceleration, rather than inhibition of carcinoma growth was observed at a dose of 100 μmol/kg. The tumor weight increased 1.5–2.0 times compared to the control values, depending on the time.

     

Suppression of in vivo tumor growth by the transfection of the interleukin-5 gene into colon tumor cells

To investigate the influence of tumor producing interleukin-5 (IL-5) on growth kinetics of tumors, we transduced the murine IL-5 gene into murine colon C26 tumor cells. Two IL-5-secreting clones, low-level IL-5 producer C26-8B and high-level IL-5 producer C26-6F, were established. Both tumors, C26-6F and C26-8B, grew more slowly than the mock C26 tumor, although the in vitro growth rate of these IL-5 transfectants was much the same as that of the mock C26 cells. There was a significantly decreased number of colonies in the lung of mice given C26-6F or C26-8B tumors i.v. than in mice given mock C26 tumors i.v. Moreover, in mice given C26-6F cells i.v., a smaller number of tumor colonies in the lung was observed, as compared to the case with C26-6B cells. While the growth rate of C26-8B tumors in mice treated with anti-IL-5 mAb was more rapid than that seen in control mAb-treated mice, growth of C26-6F tumors in anti-IL-5-mAb-treated mice was slightly more rapid compared to findings in control mAb-treated mice. The isotypematched mAb did not alter the in vitro growth of mock-C26 cells or of the IL-5-gene-modified C26 cells. Growth of IL-5-secreting C26 tumors transplanted in nude mice was also inhibited. These results suggest that tumor-producing IL-5 inhibits growth of colon tumors mediated through T-cell-independent protective mechanisms of the host.     

The Antitumor and Cytotoxic Effects of Polyacrylates of Noble Metals

We compared the antitumor and cytotoxic activities of two polyacrylic acid-based compounds containing gold (aurumacryl) and silver (argacryl). The tested substances successfully inhibit the growth of some solid tumors in mice (Lewis lung carcinoma, Acatol adenocarcinoma, and Ca-755 adenocarcinoma) and exert pronounced cytotoxic activity against human tumor cells (MCF-7 cell culture). The coefficient of murine tumor growth inhibition varies between 55 and 90% with reference to the control. The index of the cytotoxic effect, IC₅₀, is 25 μg/mL and 100 μg/mL for argacryl and aurumacryl, respectively. The sensitivity of animal tumor cells in vivo and human tumor cells in vitro to the tested substances depends on the nature of the metal coordinated in the polymer compound.

     

Elevated levels of interleukin-13 and IL-18 in patients with dengue hemorrhagic fever

Interleukin (IL)-13 is produced by T helper 2 (Th2)-type cells and inhibits the production of proinflammatory cytokines by activated monocytes, while IL-18 is a pleiotropic cytokine that induces interferon-gamma and plays an important role in the development of Th1-type cells. Role of the shift from a Th1-type response to Th2-type has been suggested in the pathogenesis of dengue hemorrhagic fever (DHF). This study was undertaken to investigate the possible protective/pathogenic role of IL-13 and IL-18 in patients with DHF. Sera were collected from a total of 84 patients with various grades of dengue illness and 21 normal healthy controls and tested for IL-13 and IL-18 levels using commercial enzyme-linked immunosorbent assay kits. The results showed that very low levels of IL-13 (4+/-3 pg ml(-1)) and IL-18 (15+/-4 pg ml(-1)) were detected in the sera of healthy controls. In dengue patients, the levels of IL-13 and IL-18 were the highest in the patients with DHF grade IV (205+/-103 pg ml(-1) and 366+/-155 pg ml(-1), respectively) and the lowest in patients with dengue fever (22+/-12 pg ml(-1) and 76+/-50 pg ml(-1), respectively). Both the cytokines appeared (IL-13=20+/-11 pg ml(-1) and IL-18=70+/-45 pg ml(-1)) during the first 4 days of illness and reached peak levels (IL-13=204+/-96 pg ml(-1) and IL-18=360+/-148 pg ml(-1)) by day 9 onwards. The presence of high levels of IL-13 and IL-18 during severe illness and late phases of the disease suggests that both of these cytokines may contribute to the shift from a Th1- to Th2-type response and thus to the pathogenesis of DHF.