苦参总黄酮体内外抗肿瘤作用实验研究

目的：考察苦参总黄酮（kushenflavonoids，KS—Fs）的体内外抗肿瘤作用。方法：采用甲基噻唑基四唑（methylthiazolyltetrazolium，MTT）比色法检测KS—Fs对多种肿瘤细胞株的生长抑制作用；构建S180肉瘤、H22肝癌和Lewis肺癌小鼠肿瘤模型和人非小细胞肺癌H460、食管癌Eca-109裸小鼠移植肿瘤模型，研究KS—Fs体内抗肿瘤作用；急性毒性试验考察KS—Fs的毒副作用。结果：KS—Fs和苦参酮（kurarinone，Kur）在体外有比苦参总碱（kushenalkaloids。KS—As）更强的细胞毒作用（半数抑制率：KSFs4．9～29．4〉g／ml，Kur2．0～13．1〉g／ml，KSAs〉200／lg／m1）。体内研究表明KSFs和Kur不仅能有效抑制小鼠H22肝癌、S180肉瘤、Lewis肺癌（瘤质量抑瘤率60％～80％），而且能显著抑制人非小细胞肺癌H460和人食管癌Eca109裸小鼠移植肿瘤的生长（瘤质量抑瘤率在41％～47％）。小鼠口服和静脉注射KS—Fs的最大耐受剂量分别大于2．8g／kg和750mg／kg，远远超过苦参碱（口服半数致死量为1．18g／kg），且无明显毒副作用。结论：研究表明KSFs或Kur是新颖的高效低毒的抗肿瘤候选药物。     

腹腔应用拓扑替康治疗人卵巢癌裸小鼠网膜移植瘤疗效观察

目的拓扑替康(TPT)静脉治疗卵巢癌疗效确切,但严重的血液学毒性反应限制了其应用.本文旨在通过体内实验探讨腹腔应用TPT治疗人卵巢癌的可行性.方法构建人卵巢癌SKOV3ipl裸小鼠网膜移植瘤模型,随机分为8组(10只/组),实验组分别腹腔注射TPT(1.5 mg/kg×2,3.0 mg/kg×2,6.0 mg/kg×2或10.0 mg/kg×1),或静脉注射TPT(6.0mg/kg×2或10.0 mg/kg×1);对照组分别腹腔注射顺铂(7.5 mg/kg)或等体积生理盐水.计算给药各组抑瘤率;用流式细胞仪评价用药后细胞周期和凋亡的改变.结果TPT疗效优于顺铂,且呈剂量与途径依赖性,其中腹腔化疗优于静脉化疗(P＜0.05),以腹腔单次大剂量TPT(10.0 mg/kg)冲击治疗效果最佳,抑瘤率达70.4%,明显优于其他各组(P＜0.05),且裸小鼠耐受性好.TPT作用于SKOV3ipl细胞周期的各个时相,与给药浓度相关.TPT诱导细胞凋亡,且凋亡的程度与拓扑替康疗效呈正相关.结论TPT腹腔化疗治疗人卵巢癌体内实验安全可行,为其临床应用打下了基础.     

BNX小鼠生物学特性及其应用

本文综述了T、B和NK细胞联合免疫缺陷BNX小鼠的培育，详细介绍其一般的生物学特性及其在血液学、肿瘤学、免疫学和微生物学等方面的应用。     

中医治疗慢性乙型肝炎的思路

慢性乙型肝炎可演变发展成肝硬化和肝癌,对人类危害极大,我国从“六五”至“七五”期间均列为国家中医学攻关研究项目。现代医学已知干扰素等可抑制肝炎病毒,但受产量和价格的限制还不能推广应用。从中医药探讨治疗本病已经取得了不少成果,但方法不一,阴转差别很大。现就从中西医结合的思路和方法探讨如下:     

BNX小鼠人胃癌原位移植模型的建立及其生物学特性的观察

目的应用T、B、NK细胞联合免疫缺陷的BNX小鼠建立人胃癌原位移植高转移模型.方法将MKN-45细胞株接种至BNX小鼠皮下,成瘤后将肿瘤组织剪成小块通过手术移植至BNX小鼠的胃壁,观察肿瘤生长与转移情况,8周后对动物进行解剖.结果胃壁原位移植瘤浸润破坏胃壁各层组织结构,并直接扩散至周围脏器.肿瘤的移植成功率为100%(23/23),表现出很高的侵袭和转移特性:原位肿瘤平均体积2837.07±1044.04 mm3,局部和远处淋巴结转移率达83%(19/23),肝转移率为83%(19/23),肺转移率为65%(15/23),膈转移率为39%(9/23),发生腹腔种植与腹水的动物为35%(8/23),此外,还有个别脾转移.结论通过T、B、NK细胞联合免疫缺陷的BNX小鼠建立人胃癌原位移植模型可以更好地模拟人胃癌侵袭与转移本身的自然过程,对人胃癌防治及其转移机理的研究提供一个更为理想的模型.     

日本2005年实验动物学会第52届年会将召开

目的探讨裸小鼠和SCID小鼠两种免疫缺陷动物人胃癌原位移植后肿瘤生长和转移等生物学特性的差异。方法将MKN-45细胞株接种至裸小鼠皮下,成瘤后采用组织学完整的组织块移植于裸小鼠和SCID小鼠胃壁建立原位移植模型,观察所建模型的原位成瘤率、移植瘤生长、侵袭和转移情况。结果①两种免疫缺陷动物的原位成瘤率都为100%;②裸小鼠原位移植瘤平均体积2884±1337mm3,腹腔淋巴结、肝、肺、膈转移率分别为67%、83%、33%和8%;③SCID小鼠原位移植瘤平均体积4582±1326 mm3(P<0.05),肝转移率90%(P>0.05),与裸小鼠较为接近, 腹腔淋巴结转移率90%,肺和膈转移率分别为100%(P<0.01)和60%(P<0.05)。结论证明应用T、B细胞联合免疫缺陷的SCID小鼠较裸小鼠更适用于建立胃癌的原位移植模型。     

腹腔与静脉应用托泊替坎治疗人卵巢癌细胞株SKOV3裸小鼠网膜移植瘤的疗效比较

Objective:To compare the therapeutic and toxic profile of topotecan given intraperitoneally with intravenously in human ovarian cancer xenografted into athymic nude mice.Methods: Eighty female Balb-c/nu-nu mice were randomized assigned into eight groups (n=10). Xeneografts resulted from intramesentery injection of cultured human ovarian cancer cells SKOV3 in athymic mice. Onset of intraperitoneal treatment with either topotecan or cisplatin (7.5 mg/kg) was on day 7. Animals scheduled for topotecan i.p. received intraperitoneal application of topotecan (1.5 mg/kg×2, 3.0 mg/kg×2, 6.0 mg/kg×2 or 10.0 mg/kg×1). Animals scheduled for topotecan i.v. received intravenous administration of topotecan (6.0 mg/kg×2 or 10.0 mg/kg×1). Two weeks after drug application animals were killed. Tumor growth inhibition were assessed and compared with untreated mice and cisplatin intraperitoneally administered mice. Acute toxicity was determined by loss of body weight. Cell cycle division and apoptosis after drug administration was determined by flow cytometric analysis.Results: In a panel of ten tumour xenografts, intraperitoneal topotecan was significantly more effective than intravenous administration. The toxicity profile suggested a better tolerability in terms of weight loss after intraperitoneal administration than cisplatin control. Topotecan 10.0 mg/kg i.p. per day (1 day) schedule was an optimal treatment for ovarian cancer and well tolerated by mice with no signs of acute toxicity. Topotecan and cisplatin induce cells G0-G1 arrest and apparent apoptosis. No significant difference among mice treated with topotecan intraperitoneally or intravenously or cisplatin was observed in term of apoptosis and cell cycle perturbation.Conclusion:The results may have implications for the future design of clinical studies on intraperitoneal application of topotecan. It suggests that apoptosis and cell cycle perturbation play an limited role in the mechanism of topotecan administration.