Antitumor activity of hot-water extract from delipidated BCG.

The antitumor activity of hot-water extract of delipidated BCG was investigated in mice inoculated with Sarcoma-180 cells and Ehrlich carcinoma cells, respectively. The hot-water extract was found to be effective when administered after and ineffective when administered before the inoculation of tumor cells. When this extract was given with anticancer drugs, such as Mitomycin C and cyclophosphamide, a combined effect was obtained in the treatment of Sarcoma-180 and of Ehrlich carcinoma.     

Antitumor activity of protoplast membrane from group A streptococcus.

Cytoplasmic membrane of Group A streptococcus has been obtained by treatment of the cells with a phage-associated lytic enzyme to dissolve the streptococcal cell wall, followed by shocking osmotically. The protoplast membrane fraction (PMF) remained as a distinct homogeneous structure in the electron micrograph and analysis showed a low rhamnose content. Febrile response produced by PMF was very slightly exhibited or not at all. PMF showed weak suppression against the growth of rat Yoshida sarcoma cells in culture and inhibition of [3H]-uridine incorporation into the sarcoma cells in vitro. In vivo antitumor experiments demonstrated that PMF has a mild inhibiting effect against mouse Ehrlich ascites carcinoma, though there was not observed a definite correlation between survival rate and dose level. Antitumor activity of PMF was thermo-labile and was strikingly abolished by treatment with a bacterial enzyme, Nagarse, but not so much by alpha-chymotrypsin.     

Antitumor cytokines]

Cytokines have various kinds of functions, including immunoregulation, host defense system, induction of inflammation and pathogenesis of many diseases. One of the characteristics of cytokines is the interaction among cytokines, and they further play an important role in the defense against tumor development, although its mechanism is highly complicated. In this paper, cytokines possessing antitumor activity, are described. These are 2 categories of antitumor cytokines, immunological and non-immunological ones. As immunological cytokines, interferons, interleukin 1, 2, 4, 5, 6, 8 and 12, tumor necrosis factor and lymphotoxin, have been investigated. On the other hand, tumor-degenerating factor, tumor regressing factor, glial maturation factor, glial growth inhibitory factor, neuroblastoma growth inhibitory factor, neonatal brain derived carcinostatic factor, chondromodulin and gliostatin have been characterized as non-immunological antitumor cytokines. These cytokines interact, and the complicated network of immunological and non-immunological antitumor cytokines is formed.     

Anticandidal low molecular compounds from higher plants with special reference to compounds from essential oils

The most active low molecular weight compounds from higher plants against Candida species are compiled from a database of antimicrobials (Amicbase) to find out new hints on their mechanism of action. The selected compounds possess strong inhibitory activities in vitro against Candida species either in the agar diffusion test, bioautography, agar dilution test, serial dilution test, or activity in the vapour phase. The test conditions are listed thoroughly and aspects of the different methods and recent developments in the testing of anticandidal drugs are discussed. The anticandidal spectra of drugs, antiseptics, and disinfectants licensed on the major markets are given for comparison of activities with compounds from natural sources. So far known mechanisms of action are described and some new structure-activity relationships are deduced from relationships between biological activities and chemical and physical parameters. Main specific targets of natural anticandidals are the ergosterol pathway, respiratory chain, and chitin biosynthesis.     

紫杉醇抗肿瘤的分子机制

目的：近年来，国内外的研究人员从不同角度对植物提取药紫杉醇的抗癌机制等方面进行了诸多研究，发现紫杉醇对多种癌细胞具有显著的疗效，对其机制的认识有助于更好的临床应用。 资料来源：本文应用计算机检索Medline数据库1979—01／2006—2期间的相关文章，检索词“Chemotherapy，tumor，taxinol”，限定文章语言种类为英文。 资料选择：选取紫杉醇机制研究和临床应用相关文献。纳入标准：①随机对照研究。②基础或临床研究包含平行对照组研究。排除标准：重复性研究或综述类文章。 资料提炼：对资料进行初审，共收集到58篇关于紫杉醇与抗肿瘤的机制研究文献。20篇为随机对照研究，且基础或临床研究包含平行对照组研究，符合纳人标准；排除38篇为重复性研究或综述类文章。 资料综合：①紫杉醇作为广谱抗癌药，对普通抗癌药物耐药的某些晚期肿瘤有良好的疗效，并且对于多种临床恶性肿瘤疗效显著而用于临床。近年的实验结果表明，紫杉醇对卡伯肉瘤细胞有显著的细胞毒作用。对P388、P1534白血病有很高的活性，能抑制W256肉瘤、S180和肺癌的生长。②紫杉醇抗肿瘤可能通过调控微管动力学稳定机制，诱导细胞凋亡机制，调控免疫机制起作用。③一般认为紫杉醇的主要靶位点是微管蛋白／微管系统，它能促进微管聚合，抑制微管降解，使细胞分裂阻滞在G2／M期，能够诱导多种癌细胞的凋亡，而大量研究表明紫杉醇对微管系统的作用及对G2／M期的阻滞并不是诱导细胞凋亡的唯一机制。④紫杉醇其药理作用新颖在于通过抑制微管蛋白和组成微管的微管蛋白二聚体动态平衡来诱导肿瘤细胞凋亡。 结论：①紫杉醇被认为是一种广谱抗癌药物，联合其他常用抗肿瘤药物，疗效可进一步提高，成为继环磷酰胺、阿霉素之后又一重要抗肿瘤药物。②可能有许多信号传导通路和机制参与紫杉醇诱导肿瘤细胞的凋亡。     

紫杉醇抗肿瘤的分子机制

目的:近年来,国内外的研究人员从不同角度对植物提取药紫杉醇的抗癌机制等方面进行了诸多研究,发现紫杉醇对多种癌细胞具有显著的疗效,对其机制的认识有助于更好的临床应用。资料来源:本文应用计算机检索Medline数据库1979-01/2006-2期间的相关文章,检索词“Chemotherapy,tumor,taxinol”,限定文章语言种类为英文。资料选择:选取紫杉醇机制研究和临床应用相关文献。纳入标准:①随机对照研究。②基础或临床研究包含平行对照组研究。排除标准:重复性研究或综述类文章。资料提炼:对资料进行初审,共收集到58篇关于紫杉醇与抗肿瘤的机制研究文献。20篇为随机对照研究,且基础或临床研究包含平行对照组研究,符合纳入标准;排除38篇为重复性研究或综述类文章。资料综合:①紫杉醇作为广谱抗癌药,对普通抗癌药物耐药的某些晚期肿瘤有良好的疗效,并且对于多种临床恶性肿瘤疗效显著而用于临床。近年的实验结果表明,紫杉醇对卡伯肉瘤细胞有显著的细胞毒作用,对P388、P1534白血病有很高的活性,能抑制W256肉瘤、S180和肺癌的生长。②紫杉醇抗肿瘤可能通过调控微管动力学稳定机制,诱导细胞凋亡机制,调控免疫机制起作用。③一般认为紫杉醇的主要靶位点是微管蛋白/微管系统,它能促进微管聚合,抑制微管降解,使细胞分裂阻滞在G2/M期,能够诱导多种癌细胞的凋亡,而大量研究表明紫杉醇对微管系统的作用及对G2/M期的阻滞并不是诱导细胞凋亡的唯一机制。④紫杉醇其药理作用新颖在于通过抑制微管蛋白和组成微管的微管蛋白二聚体动态平衡来诱导肿瘤细胞凋亡。结论:①紫杉醇被认为是一种广谱抗癌药物,联合其他常用抗肿瘤药物,疗效可进一步提高,成为继环磷酰胺、阿霉素之后又一重要抗肿瘤药物。②可能有许多信号传导通路和机制参与紫杉醇诱导肿瘤细胞的凋亡。     

Antitumor activity of some organotin complexes of hydroxamic acids derived from dibasic carboxylic acid

The sensitivities of normal and preneoplastic rat hepatocytes have been tested against four organotin hydroxamates in vitro. These organotin hydroxamates are soluble in lipids but not in aqueous medium. The solubility in lipid had initially been utilized in the pilot experiments with Ehrlich ascites tumor cells containing lipids in the ascites fluid. Cytochemical staining of protein and the growths of drug-treated cells in vivo have been studied for Ehrlich ascites tumor cells. Measurement of DNA synthesis, protein content and the cytochemical staining of protein have been employed for normal and preneoplastic hepatocytes. Ehrlich ascites tumor cells and the preneoplastic hepatocytes are markedly sensitive to organotin hydroxamates whereas the normal hepatocytes are less sensitive to these chemicals. The results of the present work are significant, and it may be worthwhile to study the further drug action in vivo.     

Antitumor activity of sphingosine kinase inhibitors

Sphingosine kinase (SK) is an oncogenic sphingolipid-metabolizing enzyme that catalyzes the formation of the mitogenic second messenger sphingosine-1-phosphate (S1P) at the expense of proapoptotic ceramide. Thus, SK is an attractive target for cancer therapy because blockage of S1P formation leads to inhibition of proliferation, as well as the induction of apoptosis in cancer cells. We have recently identified novel SK inhibitors with nanomolar to low micromolar potencies toward recombinant human SK. This study describes the continuing analysis of these inhibitors through in vitro and in vivo experiments. All three structurally diverse SK inhibitors tested showed antitumor activity in mice without exhibiting toxicity. Blood and tumor inhibitor concentrations exceeded in vitro potency levels. Cell signaling analyses in vitro revealed mixed inhibition of mitogen-activated protein kinase kinase and Akt phosphorylation by the SK inhibitors. Importantly, 4-[4-(4-chloro-phenyl)-thiazol-2-ylamino]-phenol (SKI-II) is orally bioavailable, detected in the blood for at least 8 h, and showed a significant inhibition of tumor growth in mice. These compounds are the first examples of nonlipid selective inhibitors of SK with in vivo antitumor activity and provide leads for further development of inhibitors of this important molecular target.     

链球菌制剂SM诱导人外周血淋巴细胞抗瘤活性的研究

目的：探讨链球菌制剂SM对人外周血淋巴细胞(PBL)的增殖效应及抗瘤活性。方法：将不同浓度的链球菌制剂SM(0．5KE/ml--0.015KE/ml)与正常人PBL共同孵育20小时，以MTT法检测经诱导后的人PBL的增殖效应及对K562细胞的杀伤活性，并采用生物活性检测法测定其上清中tnf-α的含量。结果：PBL与不同浓度的链球菌制剂SM作用20小时后，细胞都有不同程度的增殖，且对K562细胞的杀伤活性随之增加，尤其浓度为0．125KE/ml时最为理想。其上清中亦能检测到较高水平的TNF-α，在0．125KE/ml--0.015KE/ml时与对照组相比，P值＜0．01。结论：链球菌制剂别能增强SM的增殖效应及抗瘤活性，其作用与其药物的浓度有关。     

Potential inhibitors for SARS-CoV-2 Mpro from marine compounds

Preventing the biological activity of SARS-CoV-2 main protease using natural compounds is of great interest. In this context, using a combination of AutoDock Vina and fast pulling of ligand simulations, eleven marine fungi compounds were identified that probably play as highly potent inhibitors for preventing viral replication. In particular, four compounds including M15 (3-O-(6-O-α-l-arabinopyranosyl)-β-d-glucopyranosyl-1,4-dimethoxyxanthone), M8 (wailupemycins H), M11 (cottoquinazolines B), and M9 (wailupemycins I) adopted the predicted ligand-binding free energy of −9.87, −9.82, −9.62, and −9.35 kcal mol⁻¹, respectively, whereas the other adopted predicted ligand-binding free energies in the range from −8.54 to −8.94 kcal mol⁻¹. The results were obtained using a combination of Vina and FPL simulations. Notably, although, AutoDock4 adopted higher accurate results in comparison with Vina, Vina is proven to be a more suitable technique for rapidly screening ligand-binding affinity with a large database of compounds since it requires much smaller computing resources. Furthermore, FPL is better than Vina to classify inhibitors upon ROC-AUC analysis.

Preventing the biological activity of SARS-CoV-2 main protease using natural compounds is of great interest.     

白血病细胞系来源的树突状细胞诱导及其抗肿瘤免疫功能研究

树突状细胞（DC）在抗肿瘤免疫反应中起关键作用，但大多数白血病病病人有DC功能缺陷，在外体扩增DC并增强其抗肿瘤免疫功能及以DC为基础的肿瘤疫苗是对白血病有效的免疫治疗方法，为了探讨由不同的髓性白血病细胞诱生DC的条件及其抗白血病反应，选用HL－60，K562和THP－1细胞与不同的细胞因子组合诱生DC，以光学和电子显微镜术观察形态特征，用流式细胞术和单克隆抗体检测细胞表型，以同种混合淋巴细胞反应观察刺激淋巴细胞增殖，用^51Cr释放法检测诱生细胞的细胞术和单克隆抗体检测细胞表型，以同种混合淋巴细胞反应观察刺激淋巴细胞增殖，用^51Cr释放法检测诱生细胞的细胞毒作用，用ELISA法测定DC培养及DC＋血单个核细胞培养的血清中IL－12及INF－γ的量，结果表明，由K562，HL－60和THP－1细胞诱生的DC具有村突状细胞的形太学特征，细胞表达DC的表面分化抗原，其中GM－CSF＋IL－4＋TNF-γ刺激HL－60－DC和THP－DC和GMCSF＋IL－4＋IL－12刺激的K562－DC中有抗原表达。3种细胞诱生的DC对混合淋巴细胞反应CTL反应有强刺激细胞因子能诱导髓性白细胞产生DC，不同细胞需要不同的细胞因子和培养条件，这些DC表达抗原呈递细胞的表型具有刺激T淋巴细胞增殖和诱导CTL反应以及分泌IL－2和促进T细胞分泌INF－γ的作用。     

放射性药物与Egr-Endostatin重组质粒的协同抑瘤作用

目的探讨Egr-内皮抑素基因联合放射性药物-胶体32P对于大鼠肝癌的抑制效果。方法经局部引入基因重组质粒及胶体32P后于,7 d1、4 d2、1 d分别测肝癌的生长率,第21d测定肝癌微血管密度(MVD)、肿瘤细胞凋亡指数(AI)等指标的变化。结果各干预组的肿瘤体积生长率、MVD、AI与对照组指标相比均具有统计学差异,P均0.05-0.01,在所有干预组中,32P+Egr-Endostatin组的抑瘤效果最好,P均0.05-0.01。肝癌生长率方面,第7 d-14d,32P干预组与单纯内皮抑素基因组、Egr-内皮抑素基因组相比抑瘤效果相近,P0.05;但到达21 d时,胶体32P干预组治疗效果则明显下降。基因联合胶体32P的干预组效果均好于其它干预组,P0.05-0.01。MVD方面,32P组与其它干预组比较具有统计学差异,P0.01。AI指标,其他干预组与32P组比较具有差异,P0.05。结论 32P联合Egr-Endostatin基因协同抑瘤,可以发挥放射性药物的照射作用,Eg-1的辐射诱导增强作用及Endostatin基因的抑制肿瘤新生血管的三重作用,疗效最为确切。     

和厚朴酚的抗肿瘤作用研究进展

从传统的中草药这些天然物质中寻找安全有效的抗肿瘤药物是目前肿瘤治疗研究的一个热点。和厚朴酚作为木兰科植物厚朴的主要活性成分,通过细胞毒作用,抑制新生血管,诱导细胞分化,诱导细胞凋亡,抑制酶的合成以及抑制DNA,RNA和(或)蛋白质的合成等机制发挥了抗肿瘤的作用。