蛇毒与白细胞介素Ⅱ抗癌协同作用的观察

本文报告了蛇毒与白细胞介素Ⅱ联合使用对Ｃ５７ＢＬ／６小鼠Ｌｅｗｉｓ肺癌的抑制作用，结果表明，适当浓度的蛇毒与ＩＬ－２联合使用，明显提高抑瘤率和ＮＫ（自然杀伤细胞）活性，与单独使用蛇毒和ＩＬ－２相比，其效果具有为显著的差异（Ｐ＜０．０５）表明二者具有抗癌协同作用，为临床治疗恶性肿瘤提供新的依据。     

严重颅脑外伤对机体免疫功能的影响及其临床意义

报告３７例严重颅脑外伤患者ＰＢＬ亚群变化及细胞因子ＩＬ－２,ｓＩＬ－２,ＩＬ－６,ＩＬ－８,ＴＮＦα和Ｇ－ＣＳＦ的变化。经促分裂原ＰＨＡ刺激培养后,ＰＢＬ亚群的变化均明显低于对照组脑外伤组ＩＬ－２下降,ＴＮＦα、ＴＮＦα、ＩＬ－６及ＩＬ－８,ｓＩＬ－２Ｒ明显上升（Ｐ〈０．０１或Ｐ〈０．０５）。脑外伤感染亚组早期上述细胞因子已有明显改变。提示ＣＤ８＾＋,ＣＤ２５＾＋和ＩＬ－２,ＴＮＦα及ＩＬ－６的测     

绿茶对 Lewis 肺癌细胞攻击 C57/BL6J 小鼠胸腺细胞及其亚群影响的保护效果

绿茶对Ｌｅｗｉｓ肺癌细胞攻击Ｃ５７／ＢＬ６Ｊ小鼠胸腺细胞及其亚群影响的保护效果葛桂秀朱茂祥杨陟华龚诒芬韩驰１陈君石１（北京放射医学研究所，北京１００８５０；１中国预防医学科学院营养与食品卫生研究所，北京１０００５０）Ｌｅｗｉｓ肺癌细胞（２×１０５／０...     

腹腔镜胆囊切除术高碳酸血症时机体内环境变化研究

报道２３例ＣＯ２气腹腹腔镜胆囊切除高碳酸血症时机机的环境变化，结果：气腹后ＰａＣＯ２，ＳＢＥ，ＡＢＥ和ＳＢＣ分别为６．７４ｋＰａ，－５．８８ｍｍｏｌ／ｌ，－６．４３ｍｍｏｌ／ｌ和１９．０９ｍｍｏｌ／Ｌ，与手术前和手术后比较有极显著差异（Ｐ〈０．０１）。ＣＯ２气腹后ＩｇＧ和ＳＩＬ－２Ｒ显著高于术前（Ｐ〈０．０１），ＩｇＡＩｇＭ，Ｔ淋巴细胞亚群与手术前比较无显著差异（Ｐ〉０．０５）。气腹后ＣＩＣ显著低     

白细胞介素—2脂质体的抗肿瘤作用试验

本文建立Ｃ５７ＢＬ／６小鼠荷瘤动物模型，通过给荷瘤小鼠腹腔注射空白脂质体、单纯ＩＬ－２及ＩＬ－２脂质体来比较其在肿瘤生长中的抑制作用。结果是空白脂质体组抑瘤率为４．２６％，单纯ＩＬ－２和脂质体ＩＬ－２的抑瘤率分别为３４．０４％和５４．６０％。空白脂质体组与单纯对照组相比无显著性差异（Ｐ＞０．０５），脂质体ＩＬ－２组与单纯ＩＬ－２组之间存在显著性差异（Ｐ＜０．０５），脂质体ＩＬ－２的抑瘤率比单纯ＩＬ－２抑瘤率提高了２０．６％。     

六价铬对g12细胞gpt位点的影响

采用改良的ｇ１２细胞代替Ｖ７９细胞，研究了六价铬［Ｃｒ（Ⅵ）］对ｇｐｔ（ｘａｎｔｈｉｎｅｇｕａｎｉｎｅｐｈｏｓｐｈｏｒｉｂｏｓｙｌｔｒａｎｓｆｅｒａｓｅ，ｇｐｔ，黄嘌呤鸟嘌呤磷酸核糖转移酶）位点的影响。结果表明，Ｋ２Ｃｒ２Ｏ７在引起细胞中毒不明显的低剂量０．６２５μｍｏｌ／Ｌ（相当于铬含量６４．９９μｇ／Ｌ）即可诱发ｇ１２细胞ｇｐｔ位点的突变，且高达本底的９倍以上；较高剂量组２．５μｍｏｌ／Ｌ诱发的６－ＴＧ（６－ｔｈｉｏｇｕａ－ｎｉｎｅ，６－巯基鸟嘌呤）突变体可达本底的５０倍以上。Ｋ２Ｃｒ２Ｏ７诱发的ｇ１２细胞ｇｐｔ位点突变在０～２．５μｍｏｌ／Ｌ的Ｋ２Ｃｒ２Ｏ７范围内，具有明显的剂量－反应关系［ｙ＝２４．２７ｘ－１．７５，ｒ＝０．９９５，ｙ为突变率（ｍｕｔａｔｉｏｎｒａｔｅ），ｘ为为Ｋ２Ｃｒ２Ｏ７剂量］。但随着Ｋ２Ｃｒ２Ｏ７的浓度增高，５．０μｍｏｌ／Ｌ的Ｋ２Ｃｒ２Ｏ７组，由于细胞存活率太低，细胞数不够，达不到最后接种要求，不易继续进行。这一现象可能与Ｋ２Ｃｒ２Ｏ７的细胞毒性有关。因此，Ｋ２Ｃｒ２Ｏ７的遗传毒性及致突变性，只是在一定的剂量范围内遵循剂量反应规律。     

普拉固定治疗冠心病高脂血症的临床研究

目的 观察普拉固治疗冠心病高脂血症疗效,并与烟酸肌醇比较。方法 冠同高脂血症２９７６例随机分为：治疗组１８４例（普拉固２０ｍｇ,临睡前顿服）;对照组１１２例（烟酸肌醇０．４ｇ。３次／ｄ,口服）;２组均服药８Ｗ。结果 治疗组的ＴＣ、ＬＤＬ－Ｃ、ＡｐｏＢ１００、ＴＸＢ２明显降低,ＨＤＬ－Ｃ、ＡｐｏＡ１、６－Ｋｅｔｏ－ＰＧＦ１ａ升高（Ｐ〈０．０５）;对照组仅ＴＣ、ＴＧ和ＬＤＬ－Ｃ降低（Ｐ〈０．０５）;两     

芦丁复合物对兔实验性脑梗塞血浆中TXB2,6—Keto—PGF1α的影响

通过建立兔大脑中动脉阻塞局灶性脑缺血实验模型，测定缺血后及经芦丁复合物治疗后血浆中ＴＸＢ２、６－Ｋｅｔｏ－ＰＧＦ１α含量。结果发现ＴＸＢ２在脑梗塞后明显增高，而６－Ｋｅｔｏ－ＰＧＦ１α含量降低，经芦丁复合物治疗后ＴＸＢ２减少，６－Ｋｅｔｏ－ＰＧＦ１α增高，与缺血组比较有显著性差异（Ｐ〈０．０１）。提示芦丁复合物有明显的调节ＴＸＢ２／６－Ｋｅｔｏ－ＰＧＦ１α增高，与缺血组比较有显著性差异（Ｐ〈０．０     

博来霉素A5抑制血管生成和抗肿瘤转移作用的实验研究

目的：证实博来霉素Ａ５抑制血管生成和抗肿瘤转移作用。方法：将含有０．５μｇ博来霉素Ａ５的载体置于胚龄７ｄ的鸡胚绒毛尿囊膜（ＣＡＭ）上,４８ｈ后观察抑制血管生成情况。Ｌｅｗｉｓ肺癌皮下接种Ｃ５７ＢＬ／６小鼠６ｄ后,在移植瘤周围及其基底部多处局部注射博来霉素Ａ５,每鼠每次０．６ｍｇ,每５天１次,共３次,接种后２５ｄ处死小鼠,观察皮下移植瘤血管生成抑制民政部和对肺转移的抑制作用。     

Effects of recombinant humanen dothelial-derived interleukin-8 on hemorhagic shock in rats

目的：研究重组人内皮细胞衍生的白细胞介素－８（ＩＬ８）对失血性休克的作用．方法：大鼠股动脉放血至ＭＡＢＰ５３２ｋＰａ，维持９０ｍｉｎ，复制晚期失血性休克模型．输血后，静脉注射ＩＬ８２５０μｇ·ｋｇ－１．放免法测定血浆ＥＴ１和６ＫＰＧＦ１α含量．结果：给予ＩＬ８后，ＭＡＢＰ显著提高，休克状态改善，２ｈ存活率相应提高；休克晚期血浆ＥＴ１水平比正常明显升高（２１±４ｖｓ８２±１８ｎｇ·Ｌ－１，Ｐ＜００１），血浆６ＫＰＧＦ１α含量明显降低（１０７±１２ｖｓ１５７±１１ｎｇ·Ｌ－１，Ｐ＜００１）．ＩＬ８显著降低血浆ＥＴ１水平（１０±４ｎｇ·Ｌ－１，Ｐ＜００１），提高血浆６ＫＰＧＦ１α含量（３６８±１６ｎｇ·Ｌ－１，Ｐ＜００１）．结论：ＩＬ８具有较好的抗休克作用．     

Opposite effects on tumor growth depending on dose of Achyranthes bidentata polysaccharides in C57BL/6 mice

We report here the investigation on the effects of Achyranthes bidentata polysaccharides (ABPS) against Lewis lung cancer (LLC) in C57BL/6 mice. Depending on its doses administered in vivo, ABPS was shown to have inhibitory as well as stimulative effects on tumor growth in LLC-bearing C57BL/6 mice. ABPS at low dose could significantly inhibit LLC growth, while high dose treatment of ABPS stimulated, rather than inhibited, LLC growth in C57BL/6 mice. Tumor cell cycle analysis revealed that more tumor cells arrested at G2/M phase after daily low dose intraperitoneal injection of ABPS for consecutive 15 days. The spleen weight increased markedly in LLC-bearing C57BL/6 mice treated with high dose of ABPS. However, the spleen cytotoxicity activity was significantly despaired in mice of high dose treatment of ABPS. Furthermore, we demonstrated that the expressions of IL-6 mRNA and TNF-alpha mRNA were markedly up-regulated in spleens from mice treated with a high dose of ABPS by RT-PCR reactions, suggesting that the low dose of ABPS inhibits tumor growth via its effect on tumor cell cycle distribution, rather than activation of NK activity as previously suggested. We postulate that the stimulation of tumor growth by high dose of ABPS is associated with dysfunction of NK cell and up-regulation of IL-6 mRNA and TNF-alpha mRNA expression in murine spleen.     

OK-432肿瘤细胞疫苗对DBA/2小鼠舌癌生长抑制作用

目的利用DBA/2小鼠移植舌癌荷瘤模型,探究OK-432肿瘤细胞疫苗对舌癌的抑制作用。方法以戊二醛为交联剂,使KLN-205细胞与OK-432产生交联,制备OK-432肿瘤细胞疫苗;将DBA/2小鼠随机分为4组,每组20只,分别右侧腹部皮下注射0.9%氯化钠注射液、OK-432、灭活的KLN-205细胞、OK-432疫苗,接种KLN-205肿瘤细胞后观察对比舌癌瘤体大小,并用统计学分析其结果。结果肿瘤大小除KLN-205组与对照组间差异没有统计学意义(P=0.094)外,其余各组间差异均有统计学意义,其中OK-432疫苗组肿瘤体积均小于其他3组。结论 OK-432肿瘤细胞疫苗能抑制小鼠舌癌的生长,具有一定的抗肿瘤效应。     

Activation of macrophage function by intraperitoneal administration of the streptococcal antitumor agent OK-432

Motility, adhesiveness, IL1 production, and inhibition of tumor cell growth in vitro were examined in murine peritoneal macrophages obtained after intraperitoneal injection of a streptococcal preparation OK-432, heat-inactivated OK-432 (HI-OK-432), and thioglycollate medium (TG). By varying the interval between intraperitoneal injection of OK-432 and the harvest of peritoneal macrophages, it was found that OK-432 induced a time-dependent multi-step alteration of these properties: step I increased motility on day 1: step II increased adhesiveness on day 2; and step II increased inhibition of tumor cell growth and IL1 production. During step III, the peritoneal macrophage population, including Ia-bearing cells, increased dramatically in the peritoneal cavities of OK-432-treated mice. In contrast, injection of either HI-OK-432 or TG, which lack antitumor activity in vivo, initiated steps I and II, but not step III. The Ia-bearing macrophages induced by OK-432 showed high ability of IL1 production, but low growth inhibitory activity against tumor cells. Based on these results, OK-432 seems to be performing a dual function: eliciting a new population of macrophages to the site of injection (heat stable function), and inducing two different populations of antitumor macrophages and Ia-bearing macrophages (heat unstable function).     

Involvement of nitric oxide in anti-tumor effects of OK-432, a streptococcal anti-tumor immunotherapeutic agent

We examined the role of nitric oxide (NO) induced by OK-432, a streptococcal immunotherapeutic agent, in anti-tumor effects of the OK-432 by in vitro and in vivo experiments using an NO synthase inhibitor, N-monomethyl-l-arginine acetate (NMA). The in vitro treatment of mouse splenocytes with OK-432 increased the expression of inducible NO synthase (iNOS) gene and NO production in a dose-dependent manner. Although it is well known that OK-432 induces cytokines such as interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, both of which are known to be potent NO inducers, we observed only a partial reduction of OK-432-induced NO production with the addition of anti-IFN-gamma and/or anti-TNF-alpha neutralizing antibodies. The cytotoxicity of the splenocytes increased by in vitro OK-432 stimulation was almost completely inhibited by the treatment with NMA. OK-432 administration resulted in a marked prolongation of survival and a significant inhibition of tumor growth in syngeneic tumor-bearing mice, whereas NMA significantly inhibited the anti-tumor effects of OK-432. Although the increased cytotoxicity of adherent splenocytes derived from OK-432-treated tumor-bearing mice was almost completely inhibited by NMA, only partial inhibition by NMA was observed in the cytotoxicity of the nonadherent splenocytes. These findings strongly suggest that the iNOS/NO induced by OK-432 is intimately involved in the anti-tumor effects of OK-432.     

Antimetastatic effect of an immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis strain Aoyama B,Z-100, through the production of interleukin-12

In this study, the role of interleukin (IL)-12 on the antimetastatic effect of Z-100 was investigated using wild-type C57BL/6 mice or IL-12p40 knockout (IL-12p40 KO) mice inoculated with highly metastatic B16F10 melanoma. When C57BL/6 mice were inoculated with B16F10 melanoma (2x10(5) cells/mouse i.v.), Z-100 (10 mg/kg i.p.) significantly suppressed the pulmonary metastasis of B16F10 melanoma 14 d after tumor inoculation. On the other hand, the antimetastatic effect of Z-100 was not observed in IL-12p40 KO mice inoculated with B16F10 melanoma. These results indicate that IL-12 is essentially required for the appearance of the antimetastatic effect of Z-100. Since helper T (Th) 2 cell responses have been reported to have a role in tumor metastasis, the regulatory effect of Z-100 on the immune balance of Th1/Th2 cell responses was investigated. In both C57BL/6 mice and IL-12p40 KO mice bearing B16F10 melanoma, Th1 cytokine production (IL-2, interferon-gamma) was significantly suppressed as compared with those in normal mice. On the other hand, Th2 cytokine production (IL-4, IL-10) in these mice was increased. The administration of Z-100 (10 mg/kg i.p.) in C57BL/6 mice bearing B16F10 melanoma improved the balance of Th1/Th2 cell responses from the Th2-dominant state to the normal state. However, the improvement of Th1/Th2 cell responses by Z-100 was not observed in IL-12p40 KO mice bearing the same tumors. In addition, Z-100 significantly increased IL-12 production by macrophages in a concentration-dependent manner, while Z-100 significantly decreased IL-10 production by these cells in vitro. These results suggested that up-regulation of IL-12 production and down-regulation of IL-10 production by Z-100 are related to the improvement of Th1/Th2 cell responses from the Th2-dominant state to the normal state, which resulted in suppression of tumor metastasis.     

海参皂苷Echinoside A和ds-Echinoside A抑制小鼠Lewis肺癌生长和转移作用

目的探讨海参皂苷Echinoside A(EA)和ds-Echinoside A(DSEA)对小鼠肿瘤生长和自发肺转移的抑制作用及机制。方法建立C57BL/6J小鼠Lewis肺癌自发性肺转移模型,连续腹腔注射给药21 d,剥离原位肿瘤和双侧肺,分别称瘤重和计数肺表面转移灶结节数;采用RT-PCR法检测肿瘤组织中半胱氨酸蛋白水解酶3(Cysteine-requiring Aspartate Protease,Caspase 3)、基质金属蛋白酶-2/9(matrix metalloproteinase-2/9,MMP-2/9)、金属蛋白酶组织抑制剂-1/2(tissue inhibitor of metalloproteinase-1/2,TIMP-1/2)、乙酰肝素酶(heparanase,HPA)和血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA的表达。结果 EA和DSEA均能抑制Lewis肺癌小鼠移植瘤的生长,并显著抑制减少肺表面转移灶结节数。EA和DSEA可以显著提高荷瘤小鼠肿瘤组织中Caspase 3和TIMP-1/2mRNA的表达,降低MMP-2/9、HPA和VEGF mR-NA的表达(P<0.05,P<0.01)。结论 EA和DSEA能显著抑制小鼠Lewis肺癌生长和自发性肺转移,其机制可能与诱导肿瘤细胞凋亡,调节细胞外基质(extracellular matrix,ECM)降解相关基因的表达、抑制VEGF的释放,从而抑制肿瘤细胞的转移和血管新生有关。     

Enhancement of antitumor activity of OK-432 (picibanil) by Triton X-114 phase partitioning

OK-432 (Picibanil), a Streptococcal immunotherapeutic agent, has been used for immunotherapy of various cancers as a biological response modifier (BRM). However, OK-432 contains multiple components consisting of immunotherapeutic ones and contaminants which may weaken the effects or exert side-effects. In this study, we investigated extraction of contaminants from OK-432 using Triton X-114 (TX-114)-water phase partitioning and examined an antitumor effect of the resulting preparation. OK-432 was subjected to TX-114 partitioning to give residual precipitate designated as OK-TX-ppt. OK-TX-ppt exerted no TLR2-mediated activity, but induced interleukin (IL)-6 in human PBMC. OK-TX-ppt also induced tumor necrosis factor (TNF)-alpha, IL-10, IL-12, and interferon (IFN)-gamma in PBMC. Moreover, IFN-gamma-inducing activity of OK-TX-ppt was significantly higher and IL-10 production was lower than that of OK-432. In tumor-bearing mice model, administration of OK-TX-ppt i.p. extended the survival time of Meth-A-bearing mice compared to OK-432. OK-TX-ppt also increased the levels of IL-12 and IFN-gamma in mouse spleen cells in vitro. These results indicated that TX-114 partitioning removed some contaminants, which attenuates the antitumor effect, from OK-432 and increase the immunotherapeutic effects of OK-432.     

肺肿瘤小鼠MDSC、 Treg 及传统T 细胞变化研究

摘要： 目的 探讨肺肿瘤小鼠骨髓源性抑制细胞 （MDSC）、 调节性 T 细胞 （Treg） 和传统 T 细胞的变化及机制。方法 采用配对设计将 20 只 C57BL/6 小鼠随机均分为 Lewis 肺癌细胞注射组 （LLC 组） 和正常对照组 （NC 组）, LLC 组采用皮下注射 LLC 细胞 100 μL （1×106 ） 制备肺肿瘤小鼠模型, 对照组注射等量生理盐水。待肿瘤形成后取小鼠脾细胞, 采用流式细胞仪检测肺肿瘤小鼠 MDSC、 Treg 及 CD4+ 和 CD8+ T 细胞比例和数量变化, 膜联蛋白-V （Annexin-Ⅴ）染色检测 CD4+ 和 CD8+ T 细胞凋亡变化, 5-溴脱氧尿嘧啶核苷 （BrdU） 染色检测 CD4+ 和 CD8+ T 细胞增殖变化。结果 与 NC 组相比, LLC 组脾脏 MDSC 比例和数量明显增加, CD4+ Foxp3+ Treg 所占 CD4+ T 细胞比例和数量明显增加,而 CD4+ 和 CD8+ T 细胞所占脾细胞比例和数量明显降低 （均 P < 0.05）。与 NC 组相比, LLC 组 CD4+ 和 CD8+ T 细胞增殖明显降低, 同时 CD8+ T 细胞凋亡明显增加 （P < 0.05）。结论 MDSC 和 Treg 细胞在肺肿瘤小鼠数量增加, 同时, MDSC 和Treg 抑制 CD4+ 和CD8+ T 细胞增殖, 并促进 CD8+ T 细胞凋亡。     

螺旋藻多糖对荷瘤小鼠化疗后造血细胞增殖、凋亡及Bcl-2表达的影响

目的研究螺旋藻多糖(PSP)对肿瘤化疗后造血细胞增殖、凋亡及Bcl-2表达的影响。方法小鼠移植性实体瘤模型、用造血祖细胞体外培养、荧光和普通光学显微镜、ELISA及免疫组化方法,检测了造血细胞增殖、凋亡、Bcl-2表达及相关细胞因子含量。结果PSP明显改善了CTX引起的CFU-GM减少、造血细胞凋亡,并促进了IL-1,IL-3和GM-CSF分泌及造血细胞Bcl-2表达。结论PSP促进内源性细胞因子的分泌间接上调抗凋亡蛋白Bcl-2表达可能是其促进肿瘤化疗后造血细胞增殖并抑制其凋亡的分子机制之一。     

OK-432肿瘤疫苗对DBA/2小鼠脾脏细胞中Th1细胞因子以及TNF-α分泌的影响

目的利用DBA/2小鼠移植舌癌荷瘤模型,探讨OK-432肿瘤疫苗对DBA/2小鼠脾脏细胞中Th1细胞因子以及TNF-α分泌的影响。方法 ELISA定量检测脾脏淋巴细胞所产生的IFN-γ,IL-2,TNF-α等细胞因子的分泌水平。结果 OK-432肿瘤疫苗组中IFN-γ、IL-2以及TNF-α的含量明显高于实验对照组(P<0.05)。结论 OK-432肿瘤疫苗可刺激荷瘤小鼠脾脏细胞Th1细胞及TNF-α的分泌,增强DBA/2小鼠的抗肿瘤免疫功能。