一些抗癌药物对荷瘤小鼠血清中唾液酸含量的影响

测定荷六种小鼠肿瘤Ｓ１８０肉瘤（实体型和腹水型）,腹水肝癌,艾氏腹水瘤,白血病Ｐ３８８和Ｌｅｗｉｓ肺癌的小鼠腹水和血清中唾液酸含量,结果显示血清中唾液酸含量与肿瘤生长,肿瘤类型有关。腹水中唾液酸含量高,推测肿瘤能比正常组织产生更多唾液酸。对四种腹水肿瘤用阴离子交换树脂层板鉴定,发现ＨｅｐＡ腹水中葡萄糖代唾液酸含量明显低于其它三种腹水瘤。还研究了十几种抗癌药物对荷Ｓ１８０和Ｌｅｗｉｓ肺癌小鼠血清中唾     

灵芝中有效成分灵芝酸的抑制肿瘤作用研究

本文采用了体外肿瘤细胞培养增殖抑制试验与体内肿瘤细胞抑制试验,结果显示灵芝酸在体外对肿瘤细胞株SW620、LS180、S180的增殖具有明显的抑制作用,体内抗肿瘤疗效试验显示灵芝酸对Lewis肺癌(足趾接种)具有一定的疗效,对荷Lewis肺癌的小鼠IL-2的生成及NK细胞的免疫活性均有一定的促进作用。因此可以认为灵芝酸通过直接细胞毒作用与激活免疫体系实现抑制肿瘤作用。     

非洲乍得湖钝顶螺旋藻多糖对S_(180)腹水瘤小鼠免疫抗肿瘤作用的实验研究

采用小鼠S180腹水瘤模型,观察非洲乍得湖钝顶螺旋藻多糖不同剂量组小鼠的生存状况、瘤体外观,测定非洲乍得湖钝顶螺旋藻多糖对小鼠免疫器官指数及血清IL-2和TNF-α水平的影响,以探讨非洲乍得湖钝顶螺旋藻多糖对肿瘤的抑制作用及其对S180腹水瘤小鼠的免疫调节作用。结果表明:高、中、低三个剂量的非洲乍得湖钝顶螺旋藻多糖均能改善腹水瘤小鼠的生存状况,缩小肿瘤在体内扩散的范围;不同浓度的非洲乍得湖钝顶螺旋藻多糖组小鼠胸腺和脾脏指数均高于模型组,肝体/比均低于模型组,以中剂量组作用效果最为显著(P0.05);不同剂量的非洲乍得湖钝顶螺旋藻多糖均显著提高小鼠血清TNF-α的水平(P0.05),对IL-2含量的影响表现为三个剂量组的均高于模型组,且高、中剂量组的与模型组相比差异显著(P0.05);三种剂量组之间相比,中剂量组对IL-2和TNF-α的诱生作用最明显,与高、低剂量组相比差异均显著(P0.05)。研究结果提示,非洲乍得湖钝顶螺旋藻多糖能够促进小鼠免疫器官的生长发育从而增强免疫功能,也可通过促进小鼠免疫细胞分泌TNF-α和IL-2而发挥免疫调节作用。     

盐酸洛拉曲克在体内、外对S-180细胞株的抗增殖作用

研究合合成新型胸苷合成酶抑制剂盐酸洛拉曲克在体内、外对S－180细胞株及正常人胚肾HEK293细胞的抗增殖作用;使用MTT法测定抑制率,以提高荷腹水瘤小鼠存活时间及荷实体瘤瘤重减轻情况为指标考察盐酸洛拉曲克对S－180所致肿瘤的治疗作用。结果表明：在体外盐酸洛拉曲克对S－180肿瘤细胞株有较强的细胞毒作用,对正常细胞HEK293抑制作用较弱（P＜0.05）;体内实验显示盐酸洛拉曲克可明显提高荷腹水瘤小鼠的存活时间,减轻荷实体瘤小鼠的瘤重,疗效与氟尿嘧啶（10mg/kg）相当（P＞0.05）或更好（P＜0.05）。可见,盐酸洛拉曲克在体内、外对S－180肿瘤细胞有显著的抗增殖作用,在体外对肿瘤细胞 具有选择性的抗增殖作用。     

蜈龙抗癌颗粒对小鼠移植性肿瘤的治疗实验

目的　观察新药“蜈龙抗癌颗粒”对四种小鼠移植性肿瘤的治疗效果 ,初步探讨该制剂对小鼠的毒副作用。方法　在小鼠急性毒性试验的基础上 ,选择三个剂量对小鼠移植性肿瘤Lewis肺癌、P388白血病、S1 80 肉瘤和H2 2 肝癌进行治疗实验 ,同时检查一批治疗Lewis肺癌实验小鼠的 15项血液学指标和脾脏、胸腺的相对重量。结果与结论　“蜈龙抗癌颗粒”在生药剂量为每日每公斤体重 10、2 5、4 0g(Lewis肺癌、P388白血病 )和每日每公斤体重 15、30、5 0g(S1 80 肉瘤和H2 2 肝癌 )时 ,对小鼠移植性肿瘤有肯定的治疗效果 ,并呈良好的量效关系 ,对小鼠Lewis肺癌的治疗效果最明显。该制剂大剂量时可能对小鼠的造血系统和免疫系统有明显影响。     

常用实验动物肿瘤细胞染色体的研究——Ⅰ小鼠肉瘤180(腹水型)核型及带型分析

本文叙述了小鼠肉瘤180(腹水型)的染色体数目和分布以及形态特征。指出肉瘤180是一种超二倍体的肿瘤,染色体众数为45(24.9％),其中包含三种标记染色体:1A、1B和2M。从核型特征来看,S180与ELD、L_1、S37和NK/LY等小鼠肿瘤相类似。对肉癌180染色体进行了G-带和C-带分析,认为B染色体是双着丝点染色体。     

超强静磁场联合环磷酰胺对S180荷瘤小鼠抗肿瘤和相关生理指标的影响

实验探讨了超强静磁场(ultra strong static magnetic field,USMF)联合环磷酰胺(cyclophosphamide,CTX)连续处理,对S180荷瘤小鼠抗肿瘤、抗氧化、免疫及骨髓抑制等方面的影响。对S180肉瘤小鼠分组处理后,剥取肉瘤组织称重并进行病理检验。检测过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶的活力、总抗氧化能力,以及肝脏和肾脏中丙二醛的含量、脾脏和胸腺指数、脾脏淋巴细胞转化率、外周血中的白细胞数目和骨髓细胞的DNA含量。腹水瘤小鼠同样处理后正常饲养,记录生存时间。结果发现,USMF+CTX组的抑瘤率(72.5%)比CTX组(51.5%)提高了40.8%,生命延长率提高了1.5倍,抗氧化和免疫能力也有一定程度的增强。表明USMF结合CTX,可以协同性抑制S180荷瘤小鼠肿瘤的生长,并减轻CTX对小鼠的副作用。     

河北省石家庄市第一医院

目的:检测日间和夜间Lewis肺癌小鼠血清中内血管内皮生长因子(VEGF)水平和肺癌组织中VEGF蛋白表达的差别,探讨肿瘤血管生成的昼夜节律。方法:选择C57BL小鼠30只,制备Lewis肺癌小鼠模型后随机分为日间组(D组)和夜间组(N组),在光照-黑暗条件下饲养建立统一同步化日夜节律。随着成瘤过程,应用ElISA方法测定两组小鼠模型第0、3、5、7天血清中VEGF浓度水平;成瘤后第9天处死小鼠,应用Westeon-blot法检测瘤体中VEGF蛋白的表达,并分别进行相关分析。结果:随着成瘤过程,D组小鼠血清中VEGF浓度均显著高于N组(P<0.05);D组小鼠瘤体组织中VEGF蛋白表达灰度值(8.87±1.20)均明显高于N组(6.43±1.35),有统计学意义(P<0.05)。结论:Lewis小鼠休息期(白天)血清中VEGF浓度及瘤体中VEGF蛋白表达水平均明显高于活动期(夜间),存在着明显的日夜差异,说明肺癌组织的血管生成可能具有一定日夜节律。     

波伦鳞花软珊瑚的一种新型二萜糖甙

从中国南海波伦鳞花软珊瑚的乙醇提取物中分离和纯化得到一种浅黄色固体,经光谱分析和化学转化确定了它的化学结构,命名为波伦鳞花软珊瑚甙D(Lemnabourside D)。采用MTT法实验结果表明该化合物对腹水型肝癌(HepA),肉瘤(S180A)和艾氏腹水癌(EAC)细胞具有较强的细胞毒性。     

三叶青黄酮对荷Lewis肺癌小鼠免疫功能及肿瘤组织凋亡相关蛋白的影响

探索三叶青黄酮对荷Lewis肺癌小鼠免疫功能及肿瘤组织凋亡相关蛋白的影响。将60只小鼠随机分为对照组、模型组、三叶青黄酮高、中、低剂量组(100、50、25 mg/mL)各10只。连续干预14天后,检测各组胸腺指数、脾脏指数、移植瘤组织凋亡及凋亡相关蛋白表达,检测外周血调节性T细胞(Treg)比例。结果显示,与模型组比,三叶青黄酮高中剂量组胸腺指数、脾脏指数和移植瘤组织凋亡率升高(P<0.05),凋亡相关蛋白表达升高(P<0.05),外周血CD4+CD25+Foxp3+Treg细胞所占比例降低(P<0.05)。综上,三叶青黄酮可降低荷Lewis肺癌小鼠Treg细胞比例,提高免疫功能,诱导移植瘤组织凋亡。     

The role of copper in drug-resistant murine and human tumors

Multidrug resistance (MDR) is still a major threat to successful clinical application of cancer chemotherapy. Copper plays an important role in biological systems, and copper is also involved in carcinogenesis. In the present investigation, we addressed the question whether metal copper might be involved in drug resistance of murine and human tumors. By means of atomic absorption spectroscopy, we determined serum copper concentrations. We found that the blood serum of tumor-bearing mice contained higher amounts of copper than healthy mice with tumors. Secondly, mice bearing doxorubicin-resistant Ehrlich ascites carcinoma- or cyclophosphamide-resistant Lewis lung carcinoma contained more copper in their serum than mice bearing the corresponding drug-sensitive parental tumors. Furthermore, the analysis of patients with breast cancer, colon carcinoma or lung cancer showed that the serum copper contents were higher in patients not responding to chemotherapy when compared to patients whose tumors responded to treatment. The copper levels in serum of healthy volunteers were lower than in cancer patients irrespective of their response to chemotherapy. Our results imply that the level of serum copper may be considered as a biomarker for treatment response.     

Tumor-Specific Transplantation Resistance in Mice after Treatment of Initial Tumors with Streptococcus thermophilus

Antitumor activity observed by treatment with Streptococcus thermophilus was further investigated. The mice cured from fibrosarcoma by treatment with heat-killed preparation of S. thermophilus, when challenged with fibrosarcoma failed to take up the tumor. However, these cured mice when challenged with sarcoma-180 or Ehrlich ascites carcinoma, did not show significant changes in tumor take and/or survival compared to their respective controls. Similarly, mice cured from sarcoma-180 were challenged with fibrosarcoma, sarcoma-180 or Ehrlich ascites carcinoma. Though there was no change in the mean survival time (MST) of the dying mice regarding sarcoma-180 or Ehrlich ascites carcinoma, there was 50 and 30% increase in the number of mice that showed total regression respectively over controls. However, there was no difference in the growth rate of fibrosarcoma. Similar observations were made with mice cured from Ehrlich ascites carcinoma, challenged with these tumors. These findings thus suggest that the antitumor response was tumor-specific and that tumor-associated antigens may have a role in imparting this specificity. Bacterial treatment non-specifically augmented this primary response.     

Antitumor effect of lysine-isopeptides

Isopeptides (ε-peptides) of lysine, with a given Mw and low polydispersity (10–400 units), were synthesized to study the relationship between their chemical structure and biological effect. The designed compounds were of high purity, low polydispersity and high stereochemical purity. The effect of the compounds was tested on a human erythroleukemia cell line (K-562) and on four transplantable mouse tumors (L1210 lymphoid leukemia, P38 macrophage derived tumor, Ehrlich ascites carcinoma, Lewis lung tumor /LLT/). In case of the L1210 and P388 tumors and the Ehrlich carcinoma, survival of the animals was used as an indicator of the effect. In case of the Lewis lung tumor, the number and size of metastases in the lung and/or liver of treated and untreated mice were used as indicators. The polymers of polymerisation degree 80–120 (Mw 10.2–15.4 KD) showed the strongest antiproliferative effect both on K562 cells and the tumors growing in vivo. This effect was manifest with a significantly higher survival rate as compared to the control (L1210, P38, Ehrlich ascites), furthermore, by a decrease in the number and size of liver and lung metastases (LLT).     

激光联合环磷酰胺对荷瘤鼠脾重和外周免疫细胞数量影响的试验研究

目的:试验以小鼠S180腹水瘤为动物实验模型,对He-Ne激光照射与化疗药物联合应用对S180荷瘤鼠脾脏重量和免疫细胞数量影响作了系统性研究。方法:应用11.00J/cm2,14.67J/cm2和22.00J/cm2三种剂量He-Ne激光照射荷瘤鼠内眼角,同时联合应用化疗药物环磷酰胺,以观察其对荷瘤鼠脾脏重量和免疫细胞数量的影响。结果:健康小鼠脾脏随日龄增加呈持续上升趋势,肿瘤对照组及CYT对照组在第4d.显著升高。此后便持续下降,尤其是CYT对照组,第8d.荷瘤鼠脾脏萎缩极为严重。而CYT/He-Ne激光联合应用组小鼠脾脏在第4d.轻微下降后,便呈持续上升趋势;CYT对外周血白细胞总数、淋巴细胞数和中性幼稚细胞数有着显著的抑制作用(P<0.01,P<0.05)。CYT/He-Ne激光联合应用组白细胞总数和中性幼稚细胞数的变化较单纯CYT应用组为轻微。结论:He-Ne激光对CYT及肿瘤本身所致免疫抑制具有明显的改善效应。     

Nature of the modifying action of polyunsaturated fatty acids on the growth of transplantable tumors of different types

Modification effect of sodium salts and ethers of linolenic, arachidonic and alpha-linolenic acids on the growth of transplantable mouse tumors was examined. Polyunsaturated fatty acids (PUFA) enhanced the growth of mammary adenocarcinoma Ca-755, whereas the opposite effect was observed in mice with leukemia L-1210 and sarcoma 180. No differences in the growth of melanoma B-16 and Lewis lung carcinoma were noted in control and experimental animals. Modification effect of PUFA was significantly suppressed by prostaglandin inhibitor indomethacin and to a lesser extent by antioxidant alpha-tocopherol.     

Antineoplastic effect of mer-trichlorobisdimethylsulphoxideaminorutheniumIII against murine tumors: comparison with cisplatin and with ImH[RuIm2Cl4

An asymmetric rutheniumIII complex containing dimethylsulphoxide ligands, namely mer-trichlorobisdimethylsulphoxideaminorutheniumIII (BBR2382), has been tested in mice bearing solid metastasizing tumors. The effects of i.p. treatment with BBR2382 on primary tumor growth and on the survival time of hosts carrying s.c. or i.m. tumors have been compared to those of cisplatin and of a rutheniumIII complex with imidazole ligands, ImH[RuIm2Cl4], described as a potent antitumor agent in a number of experimental models of murine neoplasms. In mice bearing Lewis lung carcinoma, BBR2382 results as effective as cisplatin on s.c. primary tumor growth and more potent than cisplatin on the prolongation of host survival time. The combined treatment of mice bearing Lewis lung carcinoma with cisplatin and BBR2382 causes a reduction of s.c. tumors higher than that caused by each single agent; the effects on host survival time are similar to those caused by BBR2382 alone but significantly superior to those caused by cisplatin alone. In CBA mice bearing MCa mammary carcinoma, the effects of BBR2382 are slightly lower than those of cisplatin on i.m. tumors but are equivalent on host survival time. The comparison of the antineoplastic action of BBR2382 with that of ImH[RuIm2Cl4] is always in favor of the former, independently of the parameter chosen and of the tumor system used. Qualitatively, the antitumor action of BBR2382 seems different from that of cisplatin and of ImH[RuIm2Cl4]; it is supposed that this agent, like other "rutheniumIII dimethylsulphoxide" complexes, could have a particular efficacy for tumors localized in the lungs.     

小鼠S_(180)瘤细胞免疫性的初步研究

本文选用灵敏度高,特异性强的酶标免疫吸附测定法(ELISA)及A.D.C.C.测试法(Antibody Dependent Cell mediated Cytotoxicity Assay)检测到以S_(180)瘤细胞免疫的小鼠血清中有抗S_(180)瘤细胞的特异抗体。并初步探讨了S_(180)肿瘤细胞膜上的唾液酸与抗原抗体相互作用的关系。实验表明S_(180)肿瘤细胞经唾液酸酶作用,水解去除瘤细胞表面的唾液酸后,对其与特异抗体的结合反应无明显影响。这提示S_(180)瘤细胞膜表面的糖蛋白上的唾液酸未必直接参与抗原抗体的特异性结合。以上结果为进一步研究患瘤小鼠各阶段的免疫情况及寻求最佳免疫时机,为治疗肿瘤奠定了基础。     

An Experimental Study of the Pharmacokinetics of the Antitumor Drug Aurumacryl

The distribution of the antitumor drug aurumacryl (intraperitoneally injected at a dose of 100 mg/kg) in the bodies of animals with Lewis lung carcinoma was studied. The determination of aurumacryl in the tumors and organs (blood, liver, kidneys, lungs, spleen, and brain) of mice was carried out for 48 h by measuring the gold content in the test tissues using inductively coupled plasma mass spectrometry. We found the preferential accumulation of the drug in the kidneys with an extremely low gold content in the brain and a relatively uniform distribution of aurumacryl between the tumor, liver, lung, and spleen tissues.