S－180瘤苗联用BCG治疗效应的研究

本文观察荷瘤小鼠（接种１×１０５Ｓ－１８０瘤细胞）用异体同基因Ｓ－１８０瘤苗联用ＢＣＧ治疗的主动免疫试验的效应．结果表明，９０％（１８／２０）实验鼠产生迟发型皮肤赵敏反应，与对照组或单一治疗组（ＢＣＧ组、瘤苗组）相比，其生存期明显延长（Ｐ＜０．０５）和转移瘤肺结节数显著下降（Ｐ＜０．０１）．ＤＣＨ反应持久的四只小鼠显示了强的抗癌免疫反应．结果证实，采用Ｈａｎｎａ免疫方案可以提高接种１×１０５瘤细胞的荷瘤鼠抗病免疫反应，并可借ＤＣＨ皮试反应监测其ＡＳＩ疗效。     

小鼠S180肉瘤脂质体瘤苗的实验研究

作者以脂质体包裹Ｓ１８０肿瘤相关抗原制备成脂质体瘤苗，以瘤苗免疫小鼠后进行肿瘤细胞攻击试验及腹腔巨噬细胞毒试验，观察小鼠Ｓ１８０肉瘤脂质体瘤苗的免疫保护作用。结果提示，脂质体瘤苗具有一定的免疫保护作用，Ｓ１８０脂质体瘤苗免疫小鼠具有抑制Ｓ１８０肿瘤生长（Ｐ＜０．０５），延长荷瘤鼠生存期（Ｐ＜０．０１）和提高小鼠腹腔巨噬细胞的细胞毒活性（Ｐ＜０．０１）的作用，但其作用不及弗氏佐剂加肿瘤细胞匀浆组。     

小鼠移植性瘤株S180与S180A对抗癌物敏感性比较

小鼠移植性瘤株Ｓ１８０与Ｓ１８０Ａ对抗癌物敏感性比较张晓连（大连市药品检验所大连１１６０２１）小鼠移植性肿瘤的选择在肿瘤研究中有重要作用。肉瘤１８０（Ｓ１８０）与肉瘤１８０腹水型（Ｓ１８０Ａ）属同种瘤株两种类型，即实体型和腹水型，是国内目前较常见保存...     

仙人掌提取物对荷瘤S180小鼠的抑瘤作用研究

目的 观察仙人掌提取物在不同时间内对S180荷瘤小鼠的抑瘤作用。方法 用野生仙人掌进行乙醇提取且制成受试溶液,并给予昆明小鼠灌胃，1次/日,0.2ml/次/只。给药6天后，皮下种植S180肉瘤建立动物模型，分别在给药7、14、21天后处死小鼠取瘤体，称瘤体重量，结果 仙人掌提取物在接种后给药7、14天对S180荷瘤小鼠的抑瘤率各为84.11%、76.37%,分别高于其在接种后给药21天的抑瘤率（46.37%）（P〈0.01）。结论 仙人掌提取物对肿瘤发生早期具有较好的抑瘤作用。     

不同微生物佐剂S-180瘤苗的免疫效应和抑瘤作用

 目的　比较肿瘤主动特异性免疫治疗中具有佐剂作用的白色念珠菌、李斯特菌及卡介苗的免疫调节效应和抑瘤作用。方法　选择白色念珠菌、李斯特菌、卡介苗各自联合小鼠S-180肿瘤疫苗,皮下免疫接种荷瘤小鼠,检测小鼠脾细胞IL-2、IFN-产生水平,腹腔MTNF-α产生水平,观察荷瘤小鼠瘤体重量和存活期。结果　三种微生物佐剂均能协同瘤苗增强免疫小鼠IL-2、IFN-和TNF-α的产生能力(P<0.01,0.05),有效抑制足垫部移植瘤的生长,抑制率在62.8%～75.8%之间,显著高于单独注射瘤苗组(P<0.01),延长腹腔植瘤小鼠平均存活期7～14天,白色念珠菌、李斯特菌协同提高腹腔植瘤小鼠存活率20%。结论　白色念珠菌和李斯特菌与卡介苗具有同样的佐剂效应,能够协同瘤苗有效抑制肿瘤生长。     

S180腹水瘤细胞提取物与rIL-2对S180实体瘤生长影响

 利用小鼠S180腹水瘤细胞提取物与rIL－2分别单用和并用对S180实体瘤生长影响。经实验观察瘤细胞提取物组,rIL－2组,提取物与rIL－2并用组对S180实体瘤的抑制率分别为27.27％、29.75％、47.93％。采用提取物与rIL－2并用组做重复试验,结果表明此实验组对S180实体瘤生长有明显的抑瘤作用。     

利凡诺对S—180实体瘤生长的影响

本文报道利凡对小鼠Ｓ－１８０实体瘤生长的影响，经研究发现利凡诺高（４５ｍｇ／ｋｇ＾－１．ｄ＾－１），中（３０ｍｇ／ｋｇ＾－１．ｄ＾－１）低（１５ｍｇ／ｋｇ＾－１．ｄ＾－１）剂量组瘤重抑制率分别为４７．５％，２９．７５％和－２３．１４％，高剂量组和阳性药组平均瘤重明显低于对照组（Ｐ〈０．０５）。阳性药（氟尿嘧啶，１５ｍｇ／ｋｇ＾－１．ｄ＾１）组瘤重抑制率为５２．０７％，采用高剂量利凡诺重复试验三次，     

直流电结合阿霉素抑制小鼠S180实体瘤生长的实验研究

本文探讨了直流电(DC)结合阿霉素(ADM)时小鼠S_(180)实体瘤的抑制作用。ADM+DC组抑瘤率为56.79％;单用DC(3v,1h/d·3) 治疗抑瘤率为28.24％;单用ADM(5mg,kg~(-1)/d·3)抑瘤率为33.62％。ADM+DC组与DC组和ADM组相比较,P<0.05。静注等量阿霉素后最大血药浓度是电治疗时肿瘤局部注射阿霉素的2.12倍,曲线下峰面积是1、40倍,心脏最大浓度为3.56倍。本研究提示直流电和阿霉素有协同作用。在直流电治疗肿瘤时,肿瘤局部注射阿霉素不仅提高了肿瘤局部药浓度,而且较传统的静注降低了阿霉素副作用,尤其是心脏毒性。     

复合瘤苗TVPBH治疗肿瘤的临床应用研究

目的重点评价人用复合瘤苗的安全性及有效性。方法应用３０例恶性实体瘤手术切除的自身肿瘤组织制成多因素处理的病毒异种化瘤苗ＴＶＰＢＨ,对术后患者进行主动免疫治疗,以１５例患者作为对照。结果发现治疗组患者外周血ＣＤ＋４／ＣＤ＋８细胞比值及ＮＫ细胞活性在治疗后显著高于术前水平（Ｐ＜０．０１）,对照组变化不显著（Ｐ＞０．０５）;两组ＴＮＦ－α和ＩＬ－２含量在治疗前后均有显著变化（Ｐ＜０．０１）,治疗组变化辐度高于对照组（Ｐ＜０．０５）;治疗过程中未观察到明显的毒副作用;通过透射电镜还观察到瘤苗中的新城疫病毒（ＮＤＶ）对来源于消化道的肿瘤细胞易感而对乳腺来源的瘤细胞不易感。结论ＴＶＰＢＨ是一种高特异性的安全有效的免疫制剂。远期疗效在进一步观察中。     

生鹅血对小鼠移植瘤S180抑瘤作用初步实验研究

目的研究生鹅血对小鼠移植瘤S180的抑瘤作用及对生存期的影响.方法通过生鹅血对昆明纯系小鼠移植瘤S180抑瘤作用,计算抑瘤率及生鹅血对移植瘤小鼠体重、生存期的影响.结果不同计量的生鹅血对S180移植瘤接种前后小鼠体重与对照组相比无差异(P＞0.05).抑癌作用显著(P＜0.01,P＜0.02),抑瘤率分别为46.69%、51.59%、42.09%、61.05%、53.60%、53.02%、47.26%.生存率分别为37.85%、43.60%.结论初步实验证明生鹅血对S180移植瘤抑瘤作用显著,延长荷瘤小鼠生命.     

Induction of apoptosis in S-180 and S-180R tumor cells by adriamycinin vivo

Apoptosis of tumor cells have become a new standard for chemotherapy. It is useful to demonstrate induction of apoptosis in tumor cells by anti-cancer drugsin vivo. We reported the results of apoptosis induction in murine tumor cell line S-180 and it’s resistant cell line S-180R by adriamycin in different dose and different time. We found that apoptosis in S-180 cells could be induced by low dose of adriamycin, the apoptosis was started at 24 h. after the administration, and reached to 62.5% of the cells to apptosis until 72 h. Comparison with the parental cell line, only 13% of S-180R cells were apoptosed. At high dose, 20% of S-180R cells were apoptosed, whereas, almost all S-180 cells were killed in the same time. The lymphocytes were appeared in abdominal cavity of the mice after treatment of adriamycin for 24 h. It was very interested to find out that there was no lymphocyte left in the abdominal cavity of the mice with S-180R cells treated at high dose of adriamycin.     

THERPEUTIC EFFECTS ON EXPERIMENTAL METASTIC TUMOR- BEARING MICE BY QI-LE(启乐) POLYSACCHARIDE ANTITUMOR METASTASES

Objective: To study the efficiency and the mechanism of QI-LE polysaccharide (QI-LE), a new compound extracted from one kind of Chinese herbs with antiplatelet activity, against tumor metastasis in mice. Methods: QI-LE was prepared by our Lab. C57BL/6 female mice transplanted with H₂₂ liver cancer cells were administered with the agent. Then the tumor nodules, pulmonary metastasis rate, and tumor cell proliferation activity were checked. Proliferation changes of tumor cells treated with different concentrations of QI-LE were also tested. Results: High and middle dosage of QI-LE could inhibit both the lymphatic and blood systemic tumor pulmonary metastases significantly, but not the tumor cell proliferation in vitro. Conclusion: QI-LE has antitumor metastasis activity, thus may be a new candidates for antitumor metastases agents. Foundation item: This work was supported by the Science Foundation from Health Department of Shandong Province (No. 2001CAICDAI) and Chinese Medicine Administration Bureau of Shandong Province(No. 99-46). Biography: Zheng Guang-juan(1964–), female, doctor of medicine, associate professor, Shandong University of Traditional Chinese Medicine, majors in tumor pathology and immunology.     

Suppression of the immune response in tumor-bearing mice. I. Response to virus-producing tumor cells and non-virus-producing tumor cells.

Spleen cells from mice inoculated with syngeneic murine sarcoma virus (MuSV)-transformed tumor cells suppressed the mixed leukocyte reaction. Mice inoculated with virus-producing tumor cells demonstrated two types of suppression. First, an early suppression was shown to be mediated by an adherent suppressor T-cell on the basis of its sensitivity to Thy 1.2 antiserum plus complement and the absence of the early suppression in T-cell-deficient nude mice. This suppression may have been induced in response to viral antigens associated with cell surface antigens (modified self-antigens) or viremia, because it was not induced by a non-virus-producing tumor cell line. Second, a late suppression was also seen in tumor-bearing BALB/c mice. This suppression was shown to be T-cell-independent by its presence in nude mice and by its resistance to gamma-irradiation and Thy 1.2 antiserum plus complement. In addition, the late suppression was present in mice inoculated with a nonproducer clone of MuSV-transformed cells. This finding suggests that viral antigens and/or viremia is not required for induction of the late suppression.     

Modulation of immune response and tumor development in tumor-bearing mice treated by the thymic factor thymostimulin

Thymostimulin (TS), a partially purified thymic factor, has a significant impact on tumor development in C57B1/6 mice inoculated with Lewis lung carcinoma (3LL) cells, as judged by its effect on time of tumor appearance after tumor cell transplantation. In a previous study, we determined the conditions under which survival rate of the tumor-bearing mice can be significantly increased by TS treatment. In the study communicated here we analyzed host defense mechanisms that are modified by TS treatment in the tumor-bearing mice. In general, immune parameters that were increased or stimulated by the presence of the tumor were further increased in the TS-treated animals (number of lymphoid spleen cells, their response in mixed lymphocyte tumor cultures, their natural killer cell activity, and their ability to produce colony-stimulating factor), or reached earlier maximum levels (spontaneous [3H]thymidine incorporation, a reflection of in vivo spleen cell activation). Responses which reflect tumor-induced immunosuppression (proliferative response induced by phytohemagglutinin or concanavalin A stimulation) were restored to normal level by TS. Specific tumor-related reactions (specific cell-mediated cytotoxicity) were preserved in the TS-treated animals. The wide spectrum of TS effects had, nevertheless, certain elements of selectivity; e.g. colony-stimulating factor, but no interferon production is enhanced by TS in the tumor-bearing mice in diametric contrast to TS effect in Mengo virus-infected mice. The spectrum of TS effects was also dependent on the type of tumor cell used. The results indicate that the significant effect of TS on 3LL tumor development in mice is associated with a strong, multifaceted effect of TS on the immune system.     

Effect of the splenic cells of tumor-bearing mice on the allograft immune response

An earlier experimental model employing quantitative analysis of allotransplantation immune response in vivo and registration of the functional activity of immunoregulatory cells was used. It was established that syngeneic transfer of spleen cells from mice bearing 20-methylcholanthrene-induced tumors to normal intact mice modifies immune response to allogeneic cells. The effect of splenocytes was found to depend on the rate of tumor growth. Moreover, the method of syngeneic transfer (systemic application or local injection) of immunoregulatory cells appeared to be of great importance for the realization of suppressive or stimulative effect of splenocytes. Possible causes of changes in the extent and nature of the effect of lymphocytes from tumor-bearing mice on allotransplantation immune response in vivo are discussed.     

阿霉素在小鼠体内诱导S－180细胞株抗药性的实验研究

利用ＢＡＢＬ／ｃ小鼠，腹腔接种Ｓ－１８０瘤细胞，阿霉素腹腔注射治疗１５个周期培育传代，得到抗阿霉素的Ｓ－１８０细胞株（Ｓ－１８０Ｒ）。此抗药细胞对阿霉素的抗药性比亲本细胞提高６６倍。对典型的ＤＮＡ拓扑异构酶Ⅱ抑制刻ＶＰ１６（Ｅｔｏｐｏｓｉｄｅ）抗药性增加９倍。经免疫组化进一步证实，抗药细胞显示多药抗药基因（ＭＤＲｇｅｎｅ）产物Ｐ－１７０糖蛋白过表达。流式萤光细胞仪测试结果也表明抗药细胞比亲本细胞排出药物能力提高８９倍。可以肯定这是ＭＤＲ基因过表达产物所致。本工作为筛选有效逆转抗药功能的药物及其他治疗手段提供了有用的动物模型。     

Inhibition of the cellular immune response to simian virus 40 tumor cells in tumor-bearing and tumor-immune mice by concanavalin A.

The effects of in vivo-administered concanavalin A (Con A) on the kinetics of the primary and secondary cellular immune responses to simian virus 40-transformed tumor cells were investigated in BALB/c mice. Either a single initial dose of 400 mug Con A or daily doses of 50 mug depressed the cell-mediated immune response to tumor cells during the progressive growth of tumors, as determined by a radioisotopic foot-pad assay. The immune depression correlated with an increase in ultimate tumor weight. Similarly, Con A suppressed the antitumor cellular immune response in tumor-immune animals. Immune reactivity returned within 6 days after a single injection of 400 mug Con. Continuous administration 50 mug Con A resulted in a gradual decline in antitumor cellular immune responsiveness, which reached a plateau by the 5th day. Splenic lymphocytes from Con A-treated, immune mice failed to elicit a local adoptive transfer reaction; their immune responsiveness tended to return after incubation with alpha-methyl-D-pyranosyl sugars.     

山仙颗粒对S-180荷瘤小鼠T细胞活性及瘤组织中Caspase-9影响的实验研究

目的:通过建立昆明小鼠S-180荷瘤模型,观察山仙颗粒(SXG)对S-180荷瘤小鼠T细胞活性及肿瘤组织中Caspase-9表达的影响,探讨其抗肿瘤的分子机制.方法:构建S-180荷瘤小鼠模型,并随机分为5组,即空白对照组、模型组、SXG低、中、高剂量组,早晚灌胃给药,连续30天.颈椎脱臼处死小鼠,游离脾脏,剥离肿瘤组织.应用MTT比色法及免疫组织化学法分别检测荷瘤小鼠脾脏T细胞活性与S-180实体瘤组织中Caspase-9的表达.结果:SXG用药各组小鼠T细胞对于S-180细胞的抑制率均高于模型组,与模型组比较均有显著差异(P<0.01);SXG用药各组,S-180肿瘤组织中Caspase-9的表达明显上调,与模型组相比较具有显著差异(P<0.01).结论:SXG有抑制肿瘤的作用,其机制与促进Caspase-9介导的肿瘤细胞凋亡密切相关.     

Characterization of effector cells mediating antitumor activity in spleen cells of tumor-bearing mice

Antitumor activity of spleen cells from BALB/c mice bearing RL male 1 lymphoma was studied. In the Winn assay spleen cells of the tumor-bearing mice inhibited the growth of RL male 1 lymphoma. This antitumor activity of spleen cells was not detected by the in vitro cell-mediated cytotoxicity assay (4-h 51Cr release assay). The effector cells in spleen cells were T-cells which manifested asialo GM1 on their cell surfaces and were radiosensitive (1000 rads). The analysis of T-cell subsets using Lyt markers showed that the effector cells expressed the Lyt-2 antigen with a small amount of the Lyt-1 antigen on their cell surfaces. In addition antitumor activity of spleen cells of the tumor-bearing mice was weak in the early stage of tumor growth, strong in the mid-stage, and disappeared in the late stage. The mechanisms of antitumor activity of spleen cells of the tumor-bearing mice are discussed.