激光、血卟啉对小鼠S-180V肿瘤细胞膜通透性的作用及其影响因素

通过Na_2~(51)CrO_4在肿瘤细胞膜内外的分布比值的测定,观察了激光血卟啉衍生物(简称HPD)对小鼠S-180V肿瘤细胞膜通透性的作用及其影响因素:(1)通过紫外吸收光谱的测定对肿瘤细胞摄取HPD的动态过程作了观察。选择了实验所需的合适HPD浓度和作用时间,并观察到细胞悬液中血清蛋白能阻抑细胞对HPD的摄取。(2)在氦氖激光照射后即可观察到含有HPD的肿瘤细胞膜外~(51)Cr/膜内~(51)Cr的比值明显增加,而单照激光或单加HPD两组的~(51)Cr比值与正常对照组相比无明显变化。(3)上述的~(51)Cr比值变化随着照后保温时间的延长而逐渐加大。与此同时细胞形态也发生相应的变化,细胞死亡率也逐渐增加。说明除了原初的光敏反应外,还有继发的细胞损伤。(4)细胞悬液中血清蛋白的存在虽然对激光血卟啉对肿瘤细胞的杀伤作用有所减弱,但在这样条件下的光敏反应比较接近临床上治疗肿瘤的实际情况。     

环状RNA在肝细胞癌中的作用及机制

肝细胞癌（hepatocellular carcinoma,HCC）治疗困难、预后很差,是肿瘤相关死亡中的第4大癌症,严重危害人类生命健康,但其具体发病机制却仍未完全阐明。因此,探索能调控肝细胞癌发生发展,作为肝细胞癌的诊断标志物或能预测患者预后的关键分子仍十分必要。环状RNA是前体mRNA通过反向剪接产生的由3′, 5′ 磷酸二酯键首尾连接形成的共价闭合环状结构,主要有外显子circRNA（exonic circRNA,ecircRNA）、环状内含子RNA（circular intronic RNA,ciRNA）及外显子 内含子circRNA（exon-intron circRNA,EIciRNA）三大类。由于环状RNA具有普遍性、高度保守性和稳定性,其可以参与多种癌症的发生发展过程,并且可作为肿瘤的早期诊断标志物及预后因子,因此,这是一类新型且非常有潜力应用于临床诊治各阶段的分子。近年来,有大量关于环状RNA与肝细胞癌的研究。这些研究表明,环状RNA在肝细胞癌发生发展进程中发挥的作用十分重要,并且其机制多样。因此,本文主要关注环状RNA在肝细胞癌中的最新进展,总结不同环状RNA分子对于肝细胞癌细胞恶性表型、肿瘤干细胞及肿瘤微环境中免疫细胞的作用,以及其在肝细胞癌临床转移、分期、诊断、预后等各阶段中发挥的功能及其具体作用机制。此外,本文还提出了目前研究中存在的一些问题和不足,以期为未来的研究提供一些新的思路及策略。     

亚硒酸钠对肿瘤细胞膜流动性及致癌性的影响

 本文为探讨硒抗肿瘤的机理而开展了硒对小鼠腹水型肝癌(Hep.A)细胞膜流动性影响的研究。结果表明;1.腹水型肝癌细胞膜流动性明显高于正常肝细胞的膜流动性。2.硒能显著降低腹水型肝癌细胞膜的流动性,而对正常肝细胞的膜流动性没有明显影响。3.通过降低腹水型肝癌细胞膜的流动性,可降低肿瘤细胞的致癌力。     

Carbohydrate-binding proteins of tumor lines with different growth properties

Summary A tumor model system of clones of myeloproliferative sarcoma virus (MPV)-transformed rat fibroblasts (NRK) with different growth properties and metastatic potential was studied. The relationship between metastatic behavior and composition of carbohydrate-binding proteins (lectins) was analyzed by affinity chromatography. The metastatic variant differs qualitatively from its parental clone in the presence of galactoside-binding proteins at apparent molecular weights of 80 kDa, 70 kDa, 22 kDa, 18 kDa and 16 kDa and of a fucose-binding protein at apparent molecular weight of 42 kDa. The -glucosyl-binding proteins at apparent molecular weights of 67 kDa and 53 kDa and a galactoside-binding protein of apparent molecular weight of 34 kDa, however, are not detectable in the metastatic variant in comparison to its parental clone. In this respect the parental clone shows closer resemblance to the clone 5–8#1 with different growth properties and low metastatic potential than to its own metastatic variant. Furthermore, only the parental clone has a melibiose- and a mannan-binding protein of an apparent molecular weight of 64 kDa and 14 kDa, respectively. Rosette formation as model system for intercellular interaction reveals differences in the inhibition pattern with sugar between the two clones 5–8#1 and 5–20#20, whereas the metastatic variant 5–20#20 (s) exhibits drastically reduced capability to form rosettes. Initial experiments demonstrate the feasibility of drug targeting to transformed fibroblasts via carbohydrate-binding proteins.     

Comparative effectiveness of lymphotoxin anticarcinogenic and tumor cell growth-inhibitory activities

Prevention of ultraviolet radiation- or chemical carcinogen-induced morphologic transformation and inhibition of tumor-producing transformed cell growth by lymphotoxin and by normal spleen leukocytes were quantitatively compared to define the antineoplastic activity spectra of these natural immune mediators. When Syrian golden hamster embryo cells seeded for colony formation in culture dishes were treated simultaneously with carcinogen and lymphotoxin, the number of morphologically transformed cell colonies was irreversibly reduced by 50% in the presence of 6 units of lymphotoxin/ml. Lymphotoxin inhibition of tumor cell growth, however, was reversible and 50% reduction in tumor cell growth in three transformed lines required 124, 330, and 477 units/ml. Thus, the anticarcinogenic activity of lymphotoxin can be 20-fold or more greater than its tumor growth-inhibitory activity. Similarly spleen leukocytes also were more effective as an anticarcinogen than as an inhibitor of tumor cell growth, consistent with previous observations that naturally occurring spleen leukocyte antineoplastic activity may result from lymphotoxin secretion.     

Intradermal administration of lipopolysaccharide in treatment of human cancer

 Lipopolysaccharide (LPS) has been recognized as a potent antitumor agent in animal tumor models; however, its use in human cancer therapy has been limited to only one trial, in which LPS from Salmonella was given intravenously. It was not very successful because of poor tumor response and was also toxic. We originally developed LPS prepared from Pantoea agglomerans (LPSp), and this was a well-purified, small-molecular-mass (5 kDa) agent. We chose intradermal rather than intravenous administration in the hope that the former would release LPS slowly into the bloodstream, and thus be less toxic while preserving antitumor activity. In our animal tumor models, intradermal administration was indeed less toxic and more beneficial for tumor regression than intravenous administration. We made a pilot study with intradermal administration of LPSp on the treatment of ten advanced cancer patients. Five of them had evaluable tumor, which had failed earlier to respond to conventional chemotherapy. Cyclophosphamide was also administered in this trial, in anticipation of its synergistic effect with LPSp. In this study LPSp was injected intradermally into each patient twice a week, starting with an initial dose of 0.4 ng/kg, and raising it to 600 or 1800 ng/kg. A 400-mg/m² dose of cyclophosphamide was given intravenously every 2 weeks. After completion of the dose escalation, the treatment was continued for at least 4 months, and it was found that 1800 ng/kg LPSp was well tolerated. A significant level of cytokines was observed in the sera for at least 8 h. These results indicate higher tolerable doses and remarkably more continuous induction of the cytokines than were reported in a previous study by others using intravenous administration. Three of the five evaluable tumors showed a significant response to our combined therapy. Intradermally administered, LPS was less toxic and elicited a tumor response in combination with cyclophosphamide; it can thus can be applied to cancer treatment even in humans. Received: 3 August 1995 / Accepted: 2 April 1996     

Tumor suppression in Drosophila is causally related to the function of the lethal(2)tumorous imaginal discs gene,a dnaJ homolog

The Drosophila melanogaster tumor suppressor gene lethal(2)tumorous imaginal discs (l(2)tid) causes in homozygotes malignant growth of cells of the imaginal discs and the death of the mutant larvae at the time of puparium formation. We describe the molecular cloning of the 1(2)tid+ gene and its temporal expression pattern in the wild-type and mutant alleles. Germ line rescue of the tumor phenotype was achieved with a 7.0 kb Hindlll-fragment derived from the polytene chromosome band 59F5. The l(2)tid+ gene spans approximately 2.5 kb of genomic DNA. The protein coding region, 1,696 bps long, is divided by an intron into two exons. The predicted Tid⁵⁶ protein contains 518 amino acids and possesses a theoretical molecular weight of 56 kDa. It shows significant homology to all known DnaJ related proteins from bacteria, yeast, and man. The possible function of the Tid⁵⁶ protein in tumor suppression is delineated. © 1995 Wiley-Liss, Inc.     

LC－CW的抗肿瘤作用及其机理的研究

提取干酪乳酸杆菌细胞壁成分（ＬＣ－ＣＷ）,研究其抗肿瘤作用及其机理。结果表明：１００μｇＬＣ－ＣＷ,ｉｐ,连续４天,可明显抑制小鼠Ｓ１８腹水瘤移植物的生长,抑瘤率为５４％。增强ＩＬ－２诱导的ＬＡＫ杀伤活性,可明显促进小鼠ＮＫ杀伤活性,明显促进小鼠Ｔ细胞转化,促进ＣｏｎＡ和ＰＨＡ－Ｐ诱导的ＩＬ－２产生,促进ＳＩＬ－２Ｒ的减少。研究结果表明ＬＣ－ＣＷ是一种重要的抗肿瘤免疫调节因子。     

Induction of Nitric Oxide Synthase in Rat C6 Glioma Cells

Abstract: We have examined the induction of nitric oxide syhthase (NOS) activity in the rat astrocyte-derived C6 glioma cell line. In contrast to the previous results with primary astrocyte cultures, incubation of C6 cells with bacterial endotoxin lipopolysaccharide (LPS; 1 μg/ml for 24 h) did not stimulate NO₂ production. However, addition of either tumor necrosis factor-a (TNF-α) or interferon-γ (IFN-γ), cytokines that by themselves had no effect on NOS activity, imparted LPS responsiveness onto these cells in a dose-dependent manner (EC₅₀ values of 39 ng/ml of TNF-α and 9.4 U/ml of IFN-γ), and the effect of TNF-α could be further potentiated (twofold) by the presence of interleukin-1β. The simultaneous presence of TNF-α and IFN-γ yielded a greater response than either cytokine alone; however, the respective EC₅₀ values were not affected. A cytoplasmic extract from induced C6 cells catalyzed the Ca²⁺-independent conversion of l -arginine to l - citrulline, with an apparent K _m of 51.2 n M , and this activity could be blocked by l -arginine analogues in the potency order amino > methyl > nitroarginine. Immunoblot analysis revealed an apparent molecular mass of 125 kDa for the NOS protein induced in C6 cells. These results indicate that the combination of LPS plus cytokines can induce NOS activity in C6 glioma cells with properties similar to those of the enzyme expressed in primary astrocyte cultures.