毛喉萜对人肝癌细胞增殖影响的实验研究

目的　探讨毛喉萜 (Forskolin)的抗肝癌作用。方法　采用克隆形成、MTT比色法观察毛喉萜对SMMC 772 1细胞的作用 ,并利用免疫细胞化学方法检测其对rasp2 1、p5 3蛋白表达的影响。结果　毛喉萜可明显抑制SMMC 772 1细胞的增殖 ,其抑制率与剂量呈正相关 (P <0 .0 1 ) ,经毛喉萜处理后 ,rasp2 1、p5 3蛋白表达均有明显下降。结论　毛喉萜能明显抑制肝癌SMMC 772 1细胞增殖 ,其作用可能与降低rasp2 1、p5 3蛋白表达有关。     

青山抗癌注射液抑制小鼠肿瘤生长的实验研究

目的：研究青山抗癌注射液对动物移植性肿瘤生长的影响．方法：以小鼠移植性肉瘤S180和肝癌H22为模型，以顺铂(DDP)为阳性对照，生理盐水(阳)为阴性对照，观察青山抗癌注射液对肿瘤生长的影响。结果：青山抗癌注射液不同剂量组对小鼠移植性肉瘤S180和肝癌H22的生长均显示了明显的抑制作用，与NS对照组相比，P＜0.01，且呈现出量效关系．结论：青山抗癌注射液具有抑制肿瘤生长的作用.     

几种植物来源不同作用机制的抗癌药抗侵袭作用

用细胞培养法和癌细胞侵袭实验,观察几种植物来源不同作用机理的抗癌药如紫杉醇、三尖杉酯碱、高三尖杉酯碱及喜树碱^[1],对黑色素瘤高转移株B16-BL6细胞及人纤维肉瘤细胞HT-1080的细胞毒作用和抗侵袭作用。结果表明紫杉醇、三尖杉酯碱、高三尖杉酯碱及喜树碱对B16-BL6和HT-1080细胞增殖均有很强的抑制作用。紫杉醇、三尖杉酯碱及高三尖杉酯碱对B16-BL6细胞侵袭和运动也有明显的抑制作用,而喜树碱在同样浓度下对B16-BL6细胞侵袭和运动均无明显抑制。     

Chlorocarbamate-mustard-linked 1,1,2-triphenylbut-1-enes with a selective antitumor activity on mammary tumors containing estrogen receptors

Summary A 1,1,2-triphenylbut-1-ene with a 4-OH group at one C-1 phenyl ring and a chlorocarbamate mustard moiety at the second C-1 ring (compound 3) was synthesized in order to obtain a cytotoxic estrogen with a specific antitumor effect on estrogen-receptor-containing tumors. This compound was tested in comparison to the carrier (compound 1) and a compound (2) having a carbamate mustard group on both C-1 phenyl rings. The estrogen receptor affinity of compound 3 was only about one-quarter lower than that of compound 1, but much higher than that of compound 2. Compounds 2 and 3 showed only partially irreversible binding to the receptor owing to their relatively low alkylating properties. The growth inhibition of the receptor-positive MCF-7 breast cancer cell line by compound 3, but not by compound 1 or 2, was more pronounced than the inhibition of the receptor-negative line MDA. In vivo the hormone-dependent, transplantable mammary tumor MXT M3.2 of the mouse was much better inhibited by compound 3 than its hormone-resistent line MXT OVEX. Compounds 1–3 had no antiestrogenic properties in the mouse, but estrogenic activity was in the order 1>3>2. From these results and because the antitumor activity of compound 3 was superior to that of compounds 1 and 2 in the hormone-dependent tumor models, a selective, receptor-mediated cytotoxic effect of compound 3 on estrogen-receptor-positive tumors in obvious.Supported by the Deutsche Forschungsgemeinschaft, SFB 234 and the Matthias Lackas StiftungDedicated to Prof. Dr. M. F. El Etreby on the occasion of his 50th birthday     

新城疫病毒pIRHN核酸疫苗构建和表达及对肿瘤细胞的影响

目的：研究NDV HN基因抗肿瘤作用及其可能机制。方法：以 pIRES1neo为表达载体构建了 NDV HN基因的pIRHN核酸疫苗，在体外转染HeLa细胞，用间接免疫荧光和Western blot检测pIRHN在真核细胞中表达状况，用荧光显微镜、DNA琼脂糖电泳及TUNEL染色等方法，检测HN基因导致细胞死亡的类型；用3，5-二羟基甲苯法测定HeLa细胞唾液酸含量的变化。结果：pIRHN 转染HeLa细胞后，能够在真核细胞中表达，能促进肿瘤细胞死亡，其死亡方式主要以诱导细胞凋亡为主，pIRHN使 HeLa细胞唾液酸含量减少。结论：用 NDV HN基因所构建的核酸疫苗能够在真核细胞中高效表达，表达的 HN蛋白主要位于胞膜，胞浆中亦有 HN蛋白表达；pIRHN具有抗肿瘤作用，可能通过其表达产物与肿瘤细胞唾液酸受体的相互作用，发挥其抗肿瘤作用。本实验为迸一步阐明NDV抗肿瘤作用机制提供了理论依据。     

FTY720免疫抑制和抗肿瘤双重作用的研究进展

FTY720是一种来源于冬虫夏草的新型药物,通过诱导淋巴细胞凋亡和归巢而表现出良好的免疫抑制效果。 同时,FTY720还能够诱导肿瘤细胞生长停滞和凋亡,抑制肿瘤的转移。本文综述了FTY720双重作用机制的研究进展。     

香菇多糖与IL-2合用对肺癌浸润淋巴细胞抗瘤活性的影响

目的探讨香菇多糖与IL-2合用对肿瘤浸润淋巴细胞(TIL)抗瘤活性的影响。方法将TIL分别置于含IL-2或IL-2加香菇多糖培养液中培养30d,观察TIL的扩增能力、抗瘤活性的变化。结果IL-2加香菇多糖培养的Til平均扩增倍数和抗瘤活性均明显高于IL-2培养的TIL。IL-2加香菇多糖培养的TIL对自体瘤细胞,K562和Raji细胞的最大杀伤活性分别为67.18±14.73％,71.25±15.86％和66.15±15.07％;而单纯IL-2培养的TIL对各种靶细胞的最大杀伤活性分别为43.81±12.17％,50.83±13.56％和45.41±13.76％。两组相比,差异显著(P＜0.05)。结论香菇多糖与IL-2合用具有促进TIL扩增,增强其抗瘤活性的作用。     

Synthesis of new xanthenone derivatives of expected antibilharzial activity

Some new 9H-thioxanthen-9-one incorporated into heterocyclic systems such as pyridone8, pyrazoline9, pyranone11, iminopyrane12, furopyrimidine17, imidazothiazole19, thiazole21, triazine24 and other related compounds through a para imminophenyl grouping at position-1 of the thioxanthenone ring were synthesized and tested as antitumor agents, against L 1210 leukemia in mice. Some of the new compounds showed considerable antitumor activity.     

Eicosanoid-mediated Cl− secretion induced by the antitumor drug,irinotecan (CPT-11), in the rat colon

Irinotecan (CPT-11) is active against a broad range of human cancer. One of the side-effects of irinotecan is a strong diarrhoea. In order to investigate the mechanism underlying this diarrhoea, the effect of irinotecan on anion secretion across the isolated rat distal colon was studied. Irinotecan caused a concentration-dependent increase in short-circuit current (Isc). The increase in Isc was completely dependent on the presence of Cl^– ions and was supressed by furosemide and the Cl^– channel blocker NPPB (5-nitro-2-(3-phenylpropylamino)-benzoate), indicating that it is caused by a Cl^– secretion. The secretory response was inhibited by indomethacin, 1-benzylimidazole, a thromboxane synthase inhibitor, and SK&F 88046 ((N,Nbis-[7-(3-Chlorobenzeneaminosulfonyl)-1,2,3,4-tetrahydroisoquinolyl)disulfonylimide), a thromboxane A₂ receptor blocker. In isolated crypts irinotecan had no effect on the membrane potential. Consequently, the secretion induced by irinotecan is an indirect one, caused by the stimulation of eicosanoid production, e.g. thromboxane A₂, in the subepithelial tissue.     

Induction of tumour necrosis factor-α by single and repeated doses of the antitumour agent 5,6-dimethylxanthenone-4-acetic acid

5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a low-molecular-weight biological response modifier scheduled for clinical evaluation, induced synthesis of tumour necrosis factor- (TNF-) in serum of mice, with maximal activity being observed at 2–3 h after administration. At a dose of 27.5 mg/kg, DMXAA induced similar TNF- concentrations as did flavone-8-acetic acid given at its maximum tolerated dose (MTD; 330 mg/kg), whereas 8-methylxanthenone-4-acetic acid, which has no antitumour activity, did not induce serum TNF- at its MTD (440 mg/kg). The dependence of schedule on TNF- induction was studied by giving DMXAA to mice in two doses of 27.5 mg/kg each separated by different intervals. An interval of 0 (i.e 55 mg/kg given in a single dose) produced a TNF- concentration 9-fold that produced hy a single dose of 27.5 mg/kg. This dose, although higher than the MTD of 30 mg/kg, did not affect the health of mice at the time of assay (3 h). An interval of 1 day produced very low levels of serum TNF- after the second injection. An interval of 3 days produced high levels of serum TNF- after the second injection (9-fold that detected in mice receiving 27.5 mg/kg in a single dose) but no long-term toxicity, whereas an interval of 7 days produced an intermediate response. Thus, the first dose can either potentiate or suppress the TNF- response to a second dose. Mice with advanced subcutaneous colon 38 tumours were treated either with a single dose of DMXAA (27.5 mg/kg) or with a divided dose (two doses of 27.5 mg/kg given 3 days apart). Both the cure rate and the tumour-growth delay were enhanced by the divided-dose schedule. The results are relevant to the design of clinical administration schedules of DMXAA and emphasise the importance of TNF- induction in the antitumour response.This study was supported by the Auckland Division of the Cancer Society of New Zealand and by the Health Research Council of New Zealand