杏多糖粗提物对荷瘤小鼠免疫功能的影响

目的:从杏果肉中提取杏多糖粗提物,探讨其体外抑瘤功效及其机制。方法:实验于2003-06/08在新疆医科大学公共卫生学院动物实验室以S180荷瘤小鼠为研究对象,分别观察杏多糖各剂量组的抑瘤效果及对荷瘤小鼠免疫功能的影响,并以细胞免疫为主,探讨体内抑瘤作用的机制。结果:杏多糖400mg/kg剂量组对S180荷瘤小鼠肿瘤生长有抑制作用,抑瘤率为31.71%;杏多糖400mg/kg剂量组可明显增强荷瘤小鼠脾脏淋巴细胞增殖能力(P<0.05),杏多糖400mg/kg剂量组对荷瘤小鼠血清中肿瘤坏死因子α均有诱生作用,可刺激肿瘤坏死因子α接近正常水平(P<0.05)。杏多糖各剂量组白细胞介素2水平与荷瘤模型组间差异无统计学意义。结论:杏多糖粗提物具有一定的抗肿瘤作用,抑制肿瘤生长和增殖可以提高荷瘤小鼠的细胞免疫功能。     

杏多糖粗提物对荷瘤小鼠免疫功能的影响

目的：从杏果肉中提取杏多糖粗提物，探讨其体外抑瘤功效及其机制。方法：实验于2003—06／08在新疆医科大学公共卫生学院动物实验室以S180荷瘤小鼠为研究对象，分别观察杏多糖各剂量组的抑瘤效果及对荷瘤小鼠免疫功能的影响，并以细胞免疫为主，探讨体内抑瘤作用的机制。结果：杏多糖400mg／kg剂量组对S180荷瘤小鼠肿瘤生长有抑制作用，抑瘤率为31．71％；杏多糖400mg／kg剂量组可明显增强荷瘤小鼠脾脏淋巴细胞增殖能力(P&;lt;0.05)，杏多糖400mg／kg剂量组对荷瘤小鼠血清中肿瘤坏死因子α均有诱生作用，可刺激肿瘤坏死因子α接近正常水平(P&;lt;0．05)。杏多糖各剂量组白细胞介素2水平与荷瘤模型组间差异无统计学意义。结论：杏多糖粗提物具有一定的抗肿瘤作用，抑制肿瘤生长和增殖可以提高荷瘤小鼠的细胞免疫功能。     

微米中药复方抗癌一号延长荷瘤小鼠存活时间的可能机制

目的通过微米中药复方抗癌一号对小鼠S180肉瘤的治疗效果的实验研究,探讨该微米中药抑制小鼠S180肉瘤生长的可能的作用机理。方法S180肉瘤细胞接种到BALB/C小鼠皮下及腹腔,成功建立BALB/C小鼠肿瘤模型后,灌胃和腹腔注射复方抗癌一号微米中药及其提取液。结果荷瘤小鼠体内实验表明该微米中药可明显抑制肿瘤生长,减少腹水的产生,明显延长荷瘤小鼠的存活时间。肿瘤抑制率为44%,生命延长率达到41.6%。荷瘤小鼠体外实验表明该微米中药具有明显的杀死瘤细胞作用,使肿瘤细胞变性坏死。结论微米中药复方抗癌一号与其提取液相比,能更有效地抑制肿瘤生长,杀死肿瘤细胞,延长荷瘤小鼠存活时间。     

微米中药复方抗癌一号延长荷瘤小鼠存活时间的可能机制

目的 通过微米中药复方抗癌一号对小鼠S180肉瘤的治疗效果的实验研究，探讨该微米中药抑制小鼠S180肉瘤生长的可能的作用机理。方法 S180肉瘤细胞接种到BALB/C小鼠皮下及腹腔，成功建立BALB/C小鼠肿瘤模型后，灌胃和腹腔注射复方抗癌一号微米中药及其提取液。结果 荷瘤小鼠体内实验表明该微米中药可明显抑制肿瘤生长，减少腹水的产生，明显延长荷瘤小鼠的存活时间。肿瘤抑制率为44%，生命延长率达到41.6%。荷瘤小鼠体外实验表明该微米中药具有明显的杀死瘤细胞作用，使肿瘤细胞变性坏死。结论 微米中药复方抗癌一号与其提取液相比，能更有效地抑制肿瘤生长，杀死肿瘤细胞，延长荷瘤小鼠存活时间。     

加味小陷胸汤抗肿瘤作用的实验研究

目的:研究加昧小陷胸汤的抗肿瘤作用.方法:用ICR小鼠复制S180实体瘤和ESC腹水瘤模型,采用经口灌胃给药法,分别观察其对小鼠移植性肿瘤生长与荷瘤生存时间的影响;用炭粒廓清法检测其对荷瘤小鼠单核-巨噬细胞系(MPS)吞噬功能的影响.结果:加味小陷胸汤中、高剂量对S180小鼠肉瘤生长的抑制率分别为34.708%和50.31%;对荷ESC腹水瘤小鼠的生命延长率分别为43.47%和53.26%(P＜0.05);能明显促进荷瘤小鼠MPS吞噬功能(P＜0.05或＜0.01).结论:加味小陷胸汤对小鼠移植性肿瘤S180有一定抑制作用,能明显延长荷瘤小鼠存活时间,并能明显促进荷瘤小鼠非特异性细胞免疫功能.     

SBHL对小鼠免疫功能影响的实验研究

目的探讨澳洲茄胺盐酸盐（SBHL）对环磷酰胺（CTX）处理小鼠免疫功能的影响。方法 Balb/c小鼠用环磷酰胺造成免疫抑制模型,同时尾静脉注射SBHL7d,观察小鼠免疫器官重量,脾细胞特异性抗体的产生、血清凝集素滴度、溶血素CH50值、ConA刺激的小鼠脾淋巴细胞增殖和小鼠腹腔巨噬细胞吞噬功能及血清中肿瘤坏死因子α含量的变化。结果 SBHL（40 mg/kg）尾静脉注射7 d,小鼠胸腺、脾脏重量增加。ConA刺激的小鼠脾淋巴细胞增殖明显。小鼠腹腔巨噬细胞吞噬功能显著增强。给药组小鼠血凝素滴度、溶血素CH50值、TNF-α也高于对照组。结论 SBHL能明显的改善环磷酰胺抑制的小鼠免疫功能,这可能是澳洲茄胺盐酸盐抗肿瘤的另一作用机理。     

梁金菇多糖对荷瘤鼠的抗肿瘤作用和免疫功能影响

目的 :研究梁金菇多糖的抗肿瘤效果及其对荷瘤小鼠免疫功能的调节作用。方法 :建立荷瘤小鼠模型 ,观察梁金菇多糖体内的抑瘤作用 ,采用MTT法检测小鼠的脾淋巴细胞转化、NK杀伤活性及LAK杀伤活性的影响。结果 :梁金菇多糖能够明显抑制荷瘤小鼠的肿瘤生长 ,能够促进正常和荷瘤小鼠的脾淋巴细胞的转化 ,提高刺激指数 ,提高NK杀伤活性及LAK杀伤活性。结论 :梁金菇多糖提高荷瘤小鼠的免疫功能是其掏肿瘤效应的机制之一。     

β—胡萝卜素与消炎痛合用对小鼠Lewis肺癌的抑瘤及免 …

β－胡萝卜（β－Ｃ）腹腔注射给药对小鼠Ｌｅｗｉｓ肺癌有明显的抑制肿瘤生长的作用，并能明显促进小鼠脾淋巴细胞增殖的增强小鼠ＮＫ细胞活性：与消炎痛（ＩＮ）合用时增强效果更为明显。提示：β－Ｃ与ＩＮ合用抗肿瘤作用主要与增强小鼠免疫功能有关。     

桂皮醛抗肿瘤活性及对S180荷瘤小鼠免疫功能的影响

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。     

异种抗原对荷S180肉瘤小鼠肿瘤内T淋巴细胞亚群的影响

目的:评价对于小鼠为异种抗原的人A型红细胞膜免疫后序贯瘤内注射对荷S180肉瘤小鼠肿瘤生长的抑制作用及时肿瘤内T淋巴细胞亚群的影响.方法:24只荷S180肉瘤小鼠分为实验组、抗原对照组、免疫对照组及空白对照组.实验组荷瘤小鼠成瘤前应用A型人红细胞膜悬液腹腔免疫,成瘤后瘤内注射5 mg/mL A型人红细胞膜,连续注射5 d.抗原对照组,不预先免疫,瘤内注射A型人红细胞膜.免疫对照组,成瘤前预先免疫,瘤内注射生理盐水,连续注射5 d.空白对照组,不预先免疫,瘤内注射生理盐水.注射第14天处死小鼠,测量瘤重,检测肿瘤内浸润Th、CTL、Treg细胞亚群数量及IL-2的含量.结果:实验组小鼠肿瘤平均重量低于免疫对照组及空白对照组(P<0.05,P<0.01).实验组肿瘤内IL-2含量高于空白对照组(P<0.01).实验组Th细胞的比例高于其他3组(P<0.01).实验组CTL细胞比例高于免疫对照组及空白对照组(P<0.01).而Treg细胞的比例低于免疫对照组及空白对照组(P<0.01).结论:人A型红细胞膜免疫后序贯瘤内注射可抑制荷S180肉瘤小鼠肿瘤生长,并使肿瘤内部Treg细胞数量降低,Th细胞及CTL细胞数量增多,IL-2含量增加.     

Differential function of polymorphonuclear leukocytes between in vivo and in vitro in tumor-bearing mice

In the present report, we compared activities of polymorphonuclear leukocytes (PMN) such as phagocytosis and bactericidal activity in vivo with those in vitro in sarcoma 180 (S 180)-bearing mice. Mice showed a remarkable leukocytosis and in increase in PMN fraction of peripheral blood leukocytes (PBL) after intraperitoneal injection of S 180 cells. Tumor-bearing mice infected with Escherichia coli (E. coli) intravenously and intraperitoneally showed an apparent delay in the clearance of bacteria compared to the non-tumor-bearing control mice. However, PBL of tumor-bearing mice showed a high phagocytic activity against beads and a high chemiluminescence (CL) activity. Dichlorofluorescein (DCFH) oxidation capacity of peripheral blood PMN in S 180-bearing mice after stimulation with phorbol myristate acetate (PMA) was about the same or a little stronger than that in control mice. On the contrary, serum and ascites of tumor-bearing mice strongly suppressed the phagocytic and bactericidal activities of casein-induced PMN against E. coli. During the early phase of E. coli infection, serum level of complement (C3) was not depressed in tumor-bearing hosts. From these results, it is concluded that leukocytosis and activation of functions of PMN in tumor-bearing mice were observed in vitro but they were not effective for the protection in the early phase of actual E. coli infection in vivo. The delay of in vivo clearance may be accounted for by a suppressive effect of serum components in tumor-bearing mice.     

三白草提取物抑瘤作用初步研究

目的 研究三白草提取物的抑瘤作用.方法 以不同剂量三白草提取物处理肝癌H22、肉瘤S180实体瘤小鼠模型,通过检测瘤组织质量的改变计算抑瘤率;处理小鼠肝癌H22腹水瘤小鼠模型,考察提取物对腹水瘤小鼠的生命延长率,并观察其对胸腺和脾脏免疫器官质量的影响.结果 三白草提取物可抑制H22、S180实体瘤的生长(P<0.05),并具有一定的免疫促进作用;可延长H22腹水瘤小鼠的生存时间(P<0.05),提高生命延长率.结论 三白草提取物对移植性肝癌H22、肉瘤S180有抑制作用.     

Escape from immune surveillance does not result in tolerance to tumor-associated antigens

Despite expression of tumor-associated or tumor-specific antigens by most tumors, evasion of protective T-cell immunity is the rule rather than the exception. Understanding whether tumor immune escape primarily represents T-cell neglect, anergy/tolerance, or quantitative limits of an existent immune response is central to developing new strategies to enhance antitumor immunity. The authors studied the immune response to MB49, a tumor that naturally expresses HY. Immune surveillance was effective following low-dose tumor inocula, since normal female mice showed a diminished incidence and slower growth rate of MB49 compared with T-cell-depleted female mice and male mice. Following high-dose tumor inoculation, females developed large, progressive tumors but continued to demonstrate immune responses to class I and class II restricted HY epitopes. The HY reactive T cells remained capable of executing HY immune responses since T cells adoptively transferred from MB49-bearing animals mediated accelerated HY skin graft rejection compared with those taken from naive mice. Thus, MB49 does not induce immune tolerance to HY but rather escapes immune surveillance largely due to quantitative limits of the immune response. Treatment of tumor-bearing animals with rhIL7 significantly increased the number of T cells responding to HY but did not alter tumor growth rate. These results demonstrate that escape from immune surveillance does not necessarily imply immune tolerance to tumor antigens and that immunotherapy need not overcome tumor-induced tolerance per se, and suggest that substantial opportunities remain in tumor-bearing hosts to amplify weak but persistent antitumor immune responses.     

SBHL诱导宫颈癌细胞株ME180凋亡的实验研究

目的 SBHL对人宫颈癌细胞的抗肿瘤作用机制。方法观察SBHL对ME180细胞增殖抑制、观察SBHL诱导ME180细胞凋亡。结果 MTT实验发现SBHL作用ME180细胞24小时后,细胞存活率明显下降,而且随着澳洲茄胺盐酸盐浓度的增加,抑制作用增强;流式细胞仪检测SBHL可引起ME180细胞阻滞于G1期,透射电镜观察细胞超微结构呈现典型的凋亡特征。结论 SBHL可抑制ME180细胞增殖并可诱导细胞发生凋亡。     

微波组织凝固诱导荷瘤宿主的抗肿瘤效应

目的观察微波组织凝固诱导荷瘤宿主抗肿瘤效应及其有关特征。方法对荷Ｈ２２肝癌小鼠行微波组织凝固（ｍｉｃｒｏｗａｖｅｔｉｓｕｅｃｏａｇｕｌａｔｉｏｎ,ＭＴＣ）治疗。观察对Ｈ２２腹水瘤的抗击作用;二氧化硅对这种作用的影响;这种作用是否有特异性;这种作用对残存实体瘤的影响。结果微波固化治疗后荷瘤小鼠存活时间显著延长。二氧化硅腹腔注射后,荷瘤小鼠生存期在ＭＴＣ组和对照组无显著差异。ＭＴＣ处理后,荷瘤小鼠抗击Ｓ１８０肉瘤的能力增强。有残存实体瘤存在时,ＭＴＣ组与对照组相比,生存期无显著差异。结论微波组织凝固可诱导荷瘤小鼠的抗肿瘤效应。这种效应有一定的非特异性,可被二氧化硅粉末阻断。这种效应对残存实体瘤作用不大。     

Enhancement of effector cell activities in mice bearing syngeneic plasmacytoma X5563 by a biological response modifier, PSK.

We investigated the effect of PSK, a protein-bound polysaccharide obtained from Coriolus versicolor of basidiomycetes, on antitumor immunity in tumor-bearing mice. PSK prolonged significantly the life span of C3H/He mice bearing syngeneic plasmacytoma X5563 in a schedule- and dose-dependent manner. PSK was most effective when administered at 100 mg/kg every other day ten times starting from the day after tumor inoculation. The administration of PSK enhanced significantly the cytostatic activity of peritoneal exudate plastic-adherent cells and the cytolytic activity of spleen cells after in vitro incubation with mitomycin C-treated tumor cells. In addition, PSK restored the cytokine-producing capacity of spleen cells suppressed in tumor-bearing mice after in vitro incubation with mitogen. Sera from tumor-bearing mice suppressed the activity of such effector cells as well as the interleukin 2-producing capacity of spleen cells, but sera from PSK-treated tumor-bearing mice prevented this suppression. These results suggest that PSK enhances antitumor immunity by reducing immunosuppressive activity of serum from tumor-bearing mice.     

Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein

Accumulation of myeloid-derived suppressor cells (MDSCs) associated with inhibition of dendritic cell (DC) differentiation is one of the major immunological abnormalities in cancer and leads to suppression of antitumor immune responses. The molecular mechanism of this phenomenon remains unclear. We report here that STAT3-inducible up-regulation of the myeloid-related protein S100A9 enhances MDSC production in cancer. Mice lacking this protein mounted potent antitumor immune responses and rejected implanted tumors. This effect was reversed by administration of wild-type MDSCs from tumor-bearing mice to S100A9-null mice. Overexpression of S100A9 in cultured embryonic stem cells or transgenic mice inhibited the differentiation of DCs and macrophages and induced accumulation of MDSCs. This study demonstrates that tumor-induced up-regulation of S100A9 protein is critically important for accumulation of MDSCs and reveals a novel molecular mechanism of immunological abnormalities in cancer.     

Antitumor effects of interleukin-7 and adoptive immunotherapy on human colon carcinoma xenografts.

The antitumor properties of recombinant human IL-7 (rhIL-7) on a human tumor was evaluated by engrafting a human colon carcinoma into immunodeficient mice and then treating the mice with rhIL-7 and adoptively transferred human peripheral blood T cells. It was found that rhIL-7 alone had no effect on the survival of the tumor-bearing recipients. However, the combination of rhIL-7 and human T cells significantly promoted the survival of the recipients compared with mice receiving either treatment by itself. When the surviving mice were analyzed 6 mo later for the degree of human cell engraftment, the recipients receiving both rhIL-7 and human T cells had greater numbers of human CD8+ T cells in the spleens. However, the human T cells recovered from the surviving mice showed low lytic activity against the tumor in vitro. Supernatants from human T cells cultured with the tumor and rhIL-7 in vitro were found to inhibit tumor growth and were demonstrated to contain high levels of IFN-gamma. Antibodies to IFN-gamma neutralized the growth inhibition of the tumor both in vitro and in vivo demonstrating that the in vivo mechanism underlying the antitumor effects of this regimen was partly dependent on the production of IFN-gamma by the T cells and not their cytolytic capability. Interestingly, systemic administration of rhIFN-gamma to tumor-bearing mice yielded little antitumor effect suggesting that adoptive immunotherapy with rhIL-7 was superior possibly because of the continuous local release of the cytokines. Therefore, rhIL-7 may be of clinical use as an antineoplastic agent and the human/mouse model is a potentially important preclinical model for in vivo evaluation of the efficacy of this and other immunotherapies.     

Fc-mOX40L fusion protein produces complete remission and enhanced survival in 2 murine tumor models

OX40L is a member of the tumor necrosis factor superfamily that provides a costimulatory signal to CD4+ and CD8+ T cells while inhibiting the effects of suppressive CD4+ CD25+ regulatory T cells. Because of this dual activity, OX40L may provide significant antitumor immunity in tumor-bearing mice. To study its clinical potential, a fusion protein consisting of mOX40L linked to the C-terminus of the Fc fragment of immunoglobulin was genetically engineered. After demonstrating its potency in vitro, several assays were performed to evaluate its antitumor effect in comparison to the OX40 agonist antibody OX86. Dosing studies in Colon 26-bearing and renal cell carcinoma (RENCA)-bearing mice showed that although OX86 produced modest tumor regression, Fc-mOX40L produced complete remission in both tumor models. Survival studies confirmed these results and showed that Fc-mOX40L treatment produced lasting responses throughout the 5-month observation period. Flow cytometric analysis of treated and untreated tumors and tumor-draining lymph nodes identified a qualitative difference in the activity of Fc-mOX40L compared with OX86 treatment as evidenced by differences in lymphoid and macrophage populations. These studies reflect the profound therapeutic potential of Fc-mOX40L, which substantially exceeds the agonist antibody OX86 in ability to produce complete tumor remissions and promote long-term survival in solid tumor models.