Antiangiogenic activity of 2-formyl-8-hydroxy-quinolinium chloride

Tumour growth is closely related to the development of new blood vessels to supply oxygen and nutrients to cancer cells. Without the neovascular formation, tumour volumes cannot increase and undergo metastasis. Antiangiogenesis is one of the most promising approaches for antitumour therapy. The exploration of new antiangiogenic agents would be helpful in antitumour therapy. Quinoline is an aromatic nitrogen compound characterized by a double-ring structure which exhibits a benzene ring fused to pyridine at two adjacent carbon atoms. The high stability of quinoline makes it preferable in a variety of therapeutic and pharmaceutical applications, including antitumour treatment. This work is to examine the potential antiangiogenic activity of the synthetic compound 2-Formyl-8-hydroxy-quinolinium chloride. We found that 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of human umbilical vein endothelial cells in vitro. Using the diethylnitrosamine-induced hepatocarcinogenesis model, 2-Formyl-8-hydroxy-quinolinium chloride showed strong antiangiogenic activity. Furthermore, 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of large Hep3B xenografted tumour from the nude mice. We assume that 2-Formyl-8-hydroxy-quinolinium chloride could be a potential antiangiogenic and antitumour agent and it is worthwhile to further study its underlying working mechanism.     

Experimental solid tumour activity ofN-[2-(dimethylamino)ethyl]-acridine-4-carboxamide

N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide (DACA), a DNA intercalator that exerts its antitumour action through the enzyme topoisomerase II, has previously been shown to be curative against the transplantable Lewis lung adenocarcinoma growing as lung tumour nodules in mice. On the basis of this finding as well as its high in vitro activity against multidrug-resistant cell lines, DACA has been chosen for clinical trial under the auspices of the Cancer Research Campaign, United Kingdom. In the present study the activity of DACA was assessed against advanced (5-mm diameter) s.c. colon 38 adenocarcinomas in BDF₁ mice using tumour-growth delay as an end point. Its activity was found to be related positively to the total dose given and negatively to the total duration of the dose schedule. Adoption of a split-dose i.p. administration schedule or slow i.v. infusion allowed the administration of large doses without toxicity. The activity of DACA was comparable with that of 5-fluorouracil and superior to that of doxorubicin, cyclophosphamide and the experimental amsacrine analogue CI-921. Mitoxantrone, amsacrine, etoposide, teniposide and daunorubicin showed minimal activity. DACA also demonstrated significant activity against the NZM3 melanoma human cell line growing as a xenograft in athymic mice.     

中药消癌散抗肿瘤作用研究及对免疫功能的影响

消癌散明显延长ＥＡＣ小鼠生命率，并抑制Ｓ１８０小鼠体重。病理学检查：用药组肿瘤细胞周围有免疫细胞浸润。消癌散能明显增强小鼠免疫功能     

淋巴因子诱导的细胞毒细胞的体外诱导条件及其抗瘤作用

研究了细胞毒细胞(LICC)的体外诱导条件、体内外抗瘤作用及其前体细胞、效应细胞的特征。正常脾细胞(NS)与腹腔细胞(NPC)及消炎痛(INM)共育可产生LICC,最适条件为10%NPC加10~(-5)～10~(-7)mol/L INM。NPC中的Mφ通过释放细胞毒细胞分化因子(CCDF)诱导NS产生LICC活性,加入10~(-5)～10~(-7)mol/L INM可消除Mφ产生的前列腺素(PG)对LICC诱导的抑制作用。LICC的产生需IL-2和CCDF两种淋巴因子的协同作用,最适条件是10%～20%CCDF加0.3～1U/ml rIL-2。用直接和间接两种方法产生的LICC在体外具有同样的杀瘤作用。经冷靶抑制试验证实,LICC具有多克隆性质。LICC与S_(180)瘤细胞同时注入小鼠腹腔能明显延长荷瘤小鼠的存活期,表明LICC对荷瘤小鼠具保护作用。LICC的前体细胞为Thy-1~-,Lyt-2~-,效应细胞为Thy-1~+,Lyt-2~-。Lyt-1~+的Th对LICC的诱导起正向调节作用,而Lyt-2~+的Ts则起负向调节作用。     

Inhibition of Ehrlich ascites carcinoma by Manilkara zapota L. stem bark in Swiss albino mice

Objective

To evaluate the antitumor activity of Manilkara zapota (M. zapota) L. stem bark against Ehrlich ascites carcinoma (EAC) in Swiss albino mice.

Methods

The in vivo antitumour activity of the ethyl acetate extract of stem bark of M. zapota L. (EASM) was evaluated at 50, 100 and 200 mg/kg bw against EAC using mean survival time. After administration of the extract of M. zapota, viable EAC cell count and body weight in the EAC tumour hosts were observed. The animal was also observed for improvement in the haematological parameters (e.g., heamoglobin content, red and white blood cells count and differential cell count) after EASM treatment.

Results

Intraperitoneal administration of EASM reduced viable EAC cells, increased the survival time, and restored altered haematological parameters. Significant efficacy was observed for EASM at 100 mg/kg dose (P<0.05).

Conclusions

It can be concluded that the ethyl acetate extract of stem bark of M. zapota L. possesses significant antitumour activity.     

基于生物信息学途径探讨阿托伐他汀钙抗肿瘤作用的分子机制

目的基于生物信息学途径探讨与阿托伐他汀钙抗肿瘤作用相关的分子机制及生物信号通路。方法人脐静脉内皮细胞株EA.hy926分为两组,对照组加0.01%二甲基亚砜(DMSO),实验组加阿托伐他汀钙(10-5 mol/L,以0.01%DMSO溶解),共同孵育24 h,提取总RNA,用Affymetrix U133 plus 2.0全基因组表达芯片检测两组对EA.hy926细胞基因表达谱的影响。用SAM软件筛选两组之间的差异基因,应用基因富集度分析(gene set enrichment analysis,GSEA)、DAVID基因功能聚类分析软件进行通路富集分析,应用the Connectivity Map(c Map)数据库对芯片数据进行分析,并对肿瘤相关信号通路的靶基因进行RT-PCR及Westernblot验证。结果基因表达谱芯片分析显示,实验组与对照组相比,获得差异表达基因649个,其中上调基因295个,下调基因354个;GSEA富集分析提示,上调了Kruppel样转录因子等血管保护基因,下调了CCNA2、CCNE2、CCNB1和CCNB2等细胞周期相关基因,并经过RT-PCR验证。通过Cmap分析,筛选到与MS-275、trichostatin A等组蛋白去乙酰化酶抑制剂及白藜芦醇等药物有较高的相似性。结论基于生物信息学的研究发现,阿托伐他汀钙可能发挥着类似组蛋白去乙酰化酶抑制剂(HDAC inhibitors)和G1/S(开始)期及G2/M(有丝分裂)期细胞周期抑制剂的作用,为阿托伐他汀钙作为抗肿瘤药物的研究提供了可行性。     

鲨鱼软骨胶囊的抑制肿瘤实验研究

鲨鱼软骨胶囊进行了抑制肿瘤试验,结果表明,鲨鱼软骨具有抑制小鼠Ｈ２２肝癌和Ｓ１８０肉瘤的作用。