20(s)-原人参二醇、人参皂苷Rh_2及人参皂苷Rg_3抗肿瘤作用的对比

目的对比20(s)-原人参二醇(Ppd)与人参皂苷Rh2(Rh2)及人参皂苷Rg3(Rg3)的抗肿瘤作用。方法建立小鼠肝癌H22、Lewis肺癌及黑色素瘤B16三种移植瘤动物模型,将小鼠随机分成11组,对照组给予0.5%羧甲基纤维素钠,阳性药组给予环磷酰胺(CTX)30 mg/kg,Ppd、Rh2及Rg3三个剂量组均给予相应受试药25、50、100 mg/kg。阳性药组隔日腹腔注射给药1次,其余各组均每日灌胃给药1次,给药容积为20 ml/kg,连续10 d。每天记录小鼠体重,末次药后称取小鼠体重及肿瘤重量并计算肿瘤抑瘤率。结果 Ppd、Rh2及Rg3在25、50、100 mg/kg剂量下,对肝癌H22、Lewis肺癌及黑色素瘤B16均有一定的抑瘤作用,仅Ppd在50、100 mg/kg剂量下对肝癌H22、Lewis肺癌及黑色素瘤B16抑制效果明显,其抑瘤率超过40%,Rh2与Rg3的抑瘤率无明显差别。结论 Ppd、Rh2及Rg3对小鼠三种移植瘤均具有抗肿瘤活性,以Ppd的抗肿瘤作用最明显,Rh2与Rg3之间无明显差别。     

三羟基异黄酮对肝癌H22细胞移植瘤的抑制作用及机制探讨

目的探讨三羟基异黄酮抑制肝癌H22细胞移植瘤的效果及机制。方法将60只小鼠随机分为A、B、C、D、E、F组,各10只。均皮下接种肝癌H22细胞建立荷瘤小鼠模型。至肿瘤平均直径≥0．5cm时,B、C、D、E、F组分别在瘤旁隔日定时注射生理盐水、1．5mg／kg二甲基亚砜（DMSO）及含1．0．2．0、4．0mg／kg三羟基异黄酮的DMSO溶液,注射液体体积均为0．2ml。共5次。末次给药24h后断颈处死小鼠,剥离瘤体测瘤重,并检测凋亡指数（AI）及增殖细胞细胞核抗原（PCNA）。结果与其他组比较,D、E、F组小鼠瘤重均显著降低（P均〈0．05）,D、E、F组间比较,P均〉0．05。与A组相比,B、C、D、E、F组AI均增加,但D、E、F组更显著（P均〈0．01）。PCNA表达各组间相比P均〉O．05。结论三羟基异黄酮对小鼠H22移植性肿瘤具有一定抑制作用,但无剂量依赖性;其机制主要是促进细胞凋亡、抑制瘤体生长。     

苦瓜籽核糖体失活蛋白对肝癌H22细胞的抑制作用及其机制

目的探讨苦瓜籽核糖体失活蛋白(苦瓜RIP)对肝癌H22细胞的抑制作用及其机制。方法取60只清洁级ICR雄性小鼠建立H22肝癌皮下移植瘤模型,随机分为阴性对照组(Con组,12只)、苦瓜RIP组(36只)及阳性对照组(CTX组,12只)。普通饲料喂养7 d;Con组予生理盐水,RIP组各12只分别予高、中、低剂量苦瓜RIP(分别为100、50、25 mg/kg),CTX组予环磷酰胺(40 mg/kg)腹腔注射,1次/d,连用12 d。观察各组肿瘤生长情况;分离血清,ELISA法检测血清细胞因子IL-6及TNF-α表达水平。结果苦瓜RIP组及CTX组瘤重明显低于Con组(P均<0.01),苦瓜RIP组抑瘤率与剂量呈正相关(P<0.01);苦瓜RIP组及CTX组IL-6及TNF-α表达明显低于Con组(P均<0.01),表达水平与剂量呈负相关(P<0.05)。结论苦瓜RIP对H22细胞有明显的抑制作用;其机制可能为下调IL-6及TNF-α等细胞因子的表达水平。     

鲜壁虎不同部位提取液对小鼠H22肝癌体内外抑制作用

目的:探讨鲜壁虎不同部位提取液对培养的H22肝癌细胞体外抑制增殖作用和对H22实体型移植瘤小鼠的体内抑制作用,寻找有效的抗肿瘤活性成分.方法:MTT法检测高、低剂量的壁虎皮肤、头部、肌肉骨骼、内脏、尾部及全壁虎的提取液对H22肝癌细胞的体外杀伤作用.采用昆明小鼠H22移植瘤模型观察壁虎内脏高、低剂量组,去内脏壁虎高、低剂量组,全壁虎高、低剂量组的体内抑瘤活性及荷瘤小鼠胸腺和脾脏指数的变化.结果:体外实验结果显示,壁虎内脏提取液高剂量可显著抑制H22细胞的增殖,抑制率为61.6%,与其他部位的提取液相比有显著差异(P<0.01).体内抑瘤实验,5-FU组的抑瘤率为65.3%,内脏低剂量和高剂量组的抑瘤率为8.4%和16.8%,去内脏为26.3%和42.1%.全壁虎为31.6%和52.1%.去内脏壁虎的高、低剂量组和全壁虎的高、低剂量组的瘤重与模型组比较有统计学差异(P<0.05或P<0.01).全壁虎高剂量组与5-FU组的瘤重相比较无统计学差异.各壁虎组与模型组小鼠的胸腺重、胸腺指数,脾脏重、脾脏指数相比均没有明显差异.而5-FU组胸腺重、胸腺指数,脾脏重、脾脏指数较模型组和各壁虎组均明显降低(P<0.01).结论:壁虎具有良好的抗肝癌效果     

三羟基苯甲酸对H_(22)肝癌细胞荷瘤小鼠生存时间的影响

目的观察3,4,5-三羟基苯甲酸(TBA)对荷肝癌H22小鼠生存时间的影响。方法建立移植性H22肝癌细胞荷瘤小鼠模型,每组10只,TBA高、中、低剂量组TBA溶液0.50、0.25、0.13g/kg灌胃给药;对照组0.5%羧甲基纤维素钠溶液0.2ml/10g灌胃给药;环磷酰胺(CTX)组CTX20mg/kg腹腔注射,每天固定时间给药1次,连续10d,观察各组小鼠生存时间,计算生命延长率。结果 TBA和CTX组小鼠平均生存时间不同程度长于模型组,其中TBA0.25g/kg组、CTX组与模型组比较差异显著(P0.05),TBA0.50、0.13g/kg组与模型组比较差异不显著(P0.05)。CTX组和TBA组小鼠生命显著延长率分别为29.02%、9.79%、24.13%和6.29%。结论 TBA灌胃给药可以不同程度抑制H22肿瘤的生长,延长荷瘤小鼠生存时间。     

天麻多糖对H22荷瘤小鼠细胞周期及caspase蛋白活性的影响

目的探讨天麻多糖对H22荷瘤小鼠细胞周期及caspase蛋白活性的影响。方法右侧腋窝接种H22肿瘤细胞制造荷瘤小鼠模型。实验设模型组、高剂量天麻多糖组、中剂量天麻多糖组、低剂量天麻多糖组及环磷酰胺(CTX)组。造模后给予天麻多糖或环磷酰胺治疗。实验结束处死小鼠,比较各组瘤重、抑瘤率、caspase-3,8,9及细胞周期分布状况。结果天麻多糖可明显减轻瘤重,高剂量天麻多糖抑瘤率可达44.7%;与模型组比较,天麻多糖中、高剂量组可显著升高caspase-3,8,9水平及G0/G1期细胞百分数,降低G2/M期细胞百分数。结论天麻多糖对H22荷瘤小鼠具有显著的抑瘤作用,其作用机制可能与影响细胞周期分布,抑制细胞增殖并激活Caspase系统诱导肿瘤细胞凋亡有关。     

海生素对小鼠Lewis肺癌的抑制作用

目的探讨海生素抗Lewis肺癌的作用。方法采用Lewis肺癌细胞株接种C57BIM6小鼠建立Lewis肺癌模型,尾静脉给予不同剂量的海生素,观察荷瘤小鼠生命延长率（ILS）及肺重指数变化。结果海生素高、中、低剂量组ILS分别为92．8％、75．1％、46．6％,其中高、中剂量组与空白对照组比较,P均〈0．05;各用药组肺重指数均明显降低（P〈0．01）。结论海生素对Lewis肺癌有明显的抑瘤作用。     

肺痿合剂对小鼠Lewis肺癌抑瘤作用的实验研究

小鼠接种Lewis肺癌细胞后随机分为对照组、肺痿合剂低剂量组、中剂量组、高剂量组、环磷酰胺(CTX)组.各组灌胃14 d后处死,观察瘤重、肺转移数目,计算抑瘤率,检测肿瘤组织中血管内皮生长因子(VEGF)表达.发现各实验组瘤重较对照组明显减轻,肺痿合剂各组和CTX组对Lewis肺癌移植瘤均有一定的抑制作用,且能明显降低肺癌组织中VEGF表达.认为肺痿合剂可抑制小鼠Lewis肺癌生长和转移,其可能是通过抑制VEGF表达来实现的.     

温度及冻融对壁虎抗H22肝癌作用的影响

目的：研究不同炮制温度及冻融对壁虎抗肝癌效果的影响，以明确较合适的壁虎炮制方法，指导临床应用。方法：MTT法检测37℃、75℃、100℃炮制的壁虎高、低剂量提取液对H22肝癌细胞体外杀伤作用。昆明小鼠H22移植瘤模型观察不同温度（37℃、75℃、100℃）炮制的壁虎高、低剂量组及非冻融壁虎组体内抑瘤活性及荷瘤小鼠胸腺、脾脏指数变化。结果：MTT法检测显示，壁虎不同温度高、低剂量组均可抑制H22细胞的增殖（P〈0．05），高剂量组与西药抑制率差异无显著性意义（P〉0．05）。体内实验显示75℃高剂量组抑制率45．8％与模型组比较差异有显著性意义（P〈0．05）。37℃、100℃各组与模型组无统计学差异（P〉0．05）。非冻融焙壁虎与干壁虎冻干粉抑瘤率分别为49．8％和51．1％，差异无显著性意义（P〉0．05）。不同温度壁虎组，非冻融焙壁虎组，干壁虎冻干粉组与模型组小鼠的胸腺重、胸腺指数、脾脏重、脾脏指数相比均没有明显差异。而5-Fu组胸腺重、胸腺指数、脾脏重、脾脏指数较模型组和各壁虎组均明显降低（P〈0．05）。结论：体内外实验均显示75℃恒温炮制能保持壁虎抗肿瘤活性成分，是有效的炮制温度。冻融并不是壁虎保持抗肝癌活性的必要条件。     

光敏剂喜泊分对H22肝癌小鼠移植瘤的放射增敏效果

目的观察光敏剂喜泊分对H22肝癌小鼠移植瘤的放射增敏效果。方法建立H22肝癌细胞小鼠移植瘤模型,将荷瘤小鼠随机分为对照组、放疗1组、联合治疗1组、放疗2组、联合治疗2组、放疗3组、联合治疗3组,观察第14天瘤体积、抑瘤率、增敏系数、小鼠生存时间、病理、细胞凋亡等指标。结果喜泊分联合放疗能够抑制小鼠移植瘤生长,尤其联合治疗2组,第14天瘤体积明显减小、增敏系数1,有最佳增敏效果,能够明显延长小鼠生存时间,病理HE染色显示,联合治疗2组肿瘤细胞坏死数量最多,坏死范围最大,流式细胞仪检测细胞凋亡显示联合治疗2组凋亡率最高。结论喜泊分联合放疗可以有效减小瘤体积,提高抑瘤率,延长小鼠生存时间,促使细胞凋亡,具有良好的放射增敏效果。     

Effect of O-4-ethoxyl-butyl-berbamine in combination with pegylated liposomal doxorubicin on advanced hepatoma in mice

AIM: To study the synergistic effects of calmodulin (CaM) antagonist O-4-ethoxyl-butyl-berbamine (EBB) and pegylated liposomal doxorubicin (PLD) on hepatoma-22 (H(22)) in vivo. METHODS: Hepatoma model was established in 50 Balb/c mice by inoculating H(22) cells (2.5 x 10(6)) subcutaneously into the right backs of the mice. These mice were divided into 5 groups, and treated with saline only, PLD only, doxorubicin (Dox) only, PLD plus EBB and Dox plus EBB, respectively. In the treatment groups, mice were given 5 intravenous of PLD or Dox on days 0, 3, 6, 9 and 12. The first dosage of PLD or Dox was 4.5 mg/kg, the other 4 injections was 1 mg/kg. EBB (5 mg/kg) was coadministered with PLD or Dox in the corresponding groups. The effect of drugs on the life spans of hepatoma-bearing mice and tumor response to the drugs were recorded. Dox levels in the hepatoma cells were measured by a fluorescence assay. Light microscopy was performed to determine the histopathological changes in the major organs of these tumor-bearing mice. The MTT method was used to analyze the effect of Dox or PLD alone, Dox in combination with EBB, or PLD in combination with EBB on the growth of H(22) cells in an in vitro experiment. RESULTS: EBB (5 mg/kg) significantly augmented the antitumor activity of Dox or PLD, remarkably prolonged the median survival time. The median survival time was 18.2 d for control group, but 89.2 d for PLD+EBB group and 70.1 d for Dox+EBB group, respectively. However, Dox alone did not show any remarkable antitumor activity, and the median survival time was just 29.7 d. Addition of EBB to Dox or PLD significantly increased the level of Dox in H(22) cells in vivo. Moreover, EBB diminished liver toxicity of Dox and PLD. In vitro, EBB reduced the IC50 value of Dox or PLD on H(22) cells from 0.050+/-0.006 mg/L and 0.054+/-0.004 mg/L to 0.012+/-0.002 mg/L and 0.013+/-0.002 mg/L, respectively (P<0.01). CONCLUSION: EBB and liposomization could improve the therapeutic efficacy of Dox in liver cancer, while decreasing its liver toxicity.     

20(s)-原人参二醇对肝癌血管内皮生长因子及碱性成纤维细胞生长因子蛋白表达的影响

目的 探讨20(s)-原人参二醇(Ppd)对肝癌血管内皮生长因子(VEGF)及碱性成纤维细胞生长因子(bFGF)表达的影响.方法 建立肝癌动物模型,将实验动物分为五组,每组10只,分对照组、环磷酰胺组(CTX)、20(s)-原人参二醇25mg/kg、50mg/kg、100mg/kg给药组,给药二周后处死动物.称肿瘤重量及肿瘤体积,制成组织切片,以备免疫组化应用.结果 与对照组相比,给药组VEGF、bFGF表达受到抑制,肿瘤的重量及体积明显减轻,组间有显著性差异(P＜0.01).结论 提示Ppd抑制了VEGF、bFGF蛋白的表达,抑制了肿瘤生长.     

20(S)-原人参二醇对肝癌间质血管密度和肿瘤细胞增殖活性的影响

探讨20(S)-原人参二醇对肝癌间质微血管密度和肿瘤细胞增殖活性的影响。建立肝癌动物模型,将实验动物分为五组,每组10只,分对照组、环磷酰胺组、20(S)-原人参二醇25mg/kg、50mg/kg、100mg／kg给药组,给药二周后处死动物,称肿瘤重量及肿瘤体积,制成组织切片,以备免疫组化应用。与对照组相比,给药组肿瘤间质血管密度低,其细胞增殖活性亦低,肿瘤的重量及体积明显减少,组间有显著性差异(P<0．01)。提示20(S)-原人参二醇抑制了肝癌间质血管密度及肿瘤细胞增殖活性,从而抑制了肿瘤生长。     

抗真菌药对复发急性弓形虫病小鼠的保护研究

目的 了解氟康唑或伊曲康唑对复发急性弓形虫病小鼠的保护作用。方法 将感染弓形虫Prugniaud株(PRU株)2月后的ICR小鼠按以下方法进行分组:环磷酰胺组(CTX),环磷酰胺+氟康唑组(CTX+F),环磷酰胺+伊曲康唑组(CTX+I),环磷酰胺+阿奇霉素组(CTX+A),阿奇霉素浓度为250 mg/kg·d,氟康唑和伊曲康唑组根据浓度不同又分为20 mg/kg·d、30 mg/kg·d和40 mg/kg·d 3个组,同时设置正常小鼠+环磷酰胺(N+CTX)和感染组(In)对照。除In组外,其余各组每天腹腔注射环磷酰胺(100 mg/kg·d),同时CTX+F、CTX+I和CTX+A组小鼠用灌胃方法分别喂食不同浓度的氟康唑、伊曲康唑和阿奇霉素,连续用药14 d。结果 实验结束时,CTX组小鼠全部死亡, CTX+A组、N+CTX组及In组小鼠全部存活,CTX+A组与CTX组存活率有显著差异(P=0.016)。CTX组、F组、I组和A组对复发急性弓形虫病小鼠的存活情况差异及其显著(P=0.000);阿奇霉素效果好于氟康唑(P=0.001),而氟康唑作用强于伊曲康唑(P=0.000)。但是氟康唑或伊曲康唑组由于药物剂量不同所导致的存活率无显著差异。CTX组与In组、F组、I组和A组比较,小鼠脑组织包囊数量明显增加(P=0.001),但是A组、I组、F组和In组之间的包囊数差别及F组和I组各个浓度之间包囊数的差别均无统计学差异。结论 氟康唑对复发急性弓形虫病小鼠能起到一定保护作用,其可作为临床上免疫低下患者同时并发弓形虫及其他机会性真菌感染时的备选药物。     

Effects of Chai-Qin-Cheng-Qi Decoction on cefotaxime in rats with acute necrotizing pancreatitis

AIM： To investigate the effect of Chai-Qin-Cheng-Qi Decoction （CQCQD） on cefotaxime （CTX） concentration in pancreas of rats with acute necrotizing pancreatitis （ANP）. METHODS： Sixty healthy male Sprague-Dawley rats were divided randomly into an ANP group （ANP model ＋ CTX, n = 20）, treatment group （ANP model ＋ CTX ＋ CQCQD, n = 20） and control group （normal rats ＋ CTX, n = 20）. ANP models were induced by retrograde intraductal injection of 3.5% sodium taurocholate （1 mL/kg）, and the control group was injected intraductally with normal saline. All rats were injected introperitoneally with 0.42 g/kg CTX （at 12-h intervals for a continuous 72 h） at 6 h after intraductal injection. Meanwhile, the treatment group received CQCQD （20 mL/kg） intragastrically at 8-h intervals, and the ANP and control group were treated intragastrically with normal saline. At 15 min after the last CTX injection, blood and pancreas samples were collected for the determination of CTX concentration using validated high-performance liquid chromatography. Pathological changes and wet-to-dry-weight （W/D） ratio of pancreatic tissue were examined. RESULTS： Serum CTX concentrations in three groups were not significantly different. Pancreatic CTX concentration and penetration ratio were lower in ANP group vs control group （4.4 ± 0.6 μg/mL vs 18.6±1.7μg/mL, P = 0.000; 5% vs 19%, P = 0.000）, but significantly higher in treatment group vs ANP group （6.4 ± 1.7 μg/mL vs 4.4 ± 0.6 μg/mL, P = 0.020; 7% vs 5%, P = 0.048）. The histological scores and W/D ratio were significantly decreased in treatment group vs ANP and control group. CONCLUSION： CQCQD might have a promotive effect on CTX concentration in pancreatic tissues of rats with ANP.     

Effect of 2-（8-hydroxy-6-methoxy- 1-oxo- 1H-2-benzopyran-3yl） propionic acid in combination with carboplatin on gastric carcinoma growth in vivo

AIM： To investigate the effects of 2-（8-hydroxy-6- methoxy-l-oxo-lH-2-benzopyran-3-yl） propionic acid （NM-3） alone and in combination with carboplatin on tumor growth and apoptosis in mouse models of human gastric cancer constructed by subcutaneous implantation of histologically intact tumor tissue.
METHODS： Human gastric cancer SGC-7901 tissues were implanted into the dorsal subcutis of nude mice. One week after tumors reached to a volume of 50-100 mm3 for around 1 wk, these mice were randomly divided into 8 groups （n = 10）. NM-3 was injected peritoneally at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg every other day for 5 wk, combined with carboplatin （5 mg/kg） every third day for 4 wk. As controls of combined treatment, another 4 groups of mice were injected with either NM-3 at 10 mg/kg, 20 mg/kg or 40 mg/kg, or with carboplatin alone （5 mg/kg）. The control mice received normal saline. Tumor weight, tumor growth inhibition （TGI）, and intratumoral microvessel density （MVD） were evaluated. Apoptosis of human gastric cancer was detected by TUNEL method and flow o/tometry analysis, respectively.
RESULTS： The mean tumor volume （692.40 ± 58.43 mm3, 548.30 ± 66.02 mm3, 382.13 ± 43.52 mm3） after treatment with carboplatin combined NM-3 at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg was lower than that after treatment with either NM-3 at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg or with carboplatin alone. Compared with the normal saline group, NM-3 administered at 10 mg/kg, 20 mg/kg or 40 mg/kg significantly reduced the tumor weight in these groups （P 〈 0.05）. Carboplatin used alone at 5 mg/kg showed minimal effects. But NM-3 in combination with carboplatin had greater effects of tumor weight than either NM-3 or carboplatin alone. NM-3 alone at the dose 10 mg/kg or in combination with carboplatin had no obvious effects on body changes. Two mice died of diarrhea in each of the two groups treated with 40 mg/kg NM-3 or with 40 mg/kg NM-3 in combination with carboplatin. A     

Effects of recombinant human canstatin protein in the treatment of pancreatic cancer

INTRODUCTION The prognosis of patients with pancreatic cancer is poor, with or without treatment. The American National Cancer Institute (NCI) reported in its SEER Cancer Statistics Review that there are approximately 27 000 new cases of pancreatic cancer…     

Effect of resveratrol and in combination with 5-FU on murine liver cancer

AIM: To study the anti-tumor effect of resveratrol and in combination with 5-FU on murine liver cancer. METHODS: Transplantable murine hepatoma22 model was used to evaluate the anti-tumor activity of resveratrol (RES) alone or in combination with 5-FU in vivo. H22 cell cycles were analyzed with flow cytometry. RESULTS: Resveratrol could inhibit the growth of murine hepatoma22, after the mice bearing H22 tumor were treated with 10 mg/kg or 15 mg/kg resveratrol for ten days, and the inhibition rates were 36.3% (n = 10) and 49.3% (n = 9), respectively, which increased obviously compared with that in control group (85+/-22 vs 68+/-17, P<0.01). RES could induce the S phase arrest of H22 cells, and increase the percentage of cells in S phase from 59.1% (n = 9) to 73.5% (n = 9) in a dose-dependent manner (P<0.05). The enhanced inhibition of tumor growth by 5-FU was also observed in hepatoma22 bearing mice when 5-FU was administered in combination with 10 mg/kg resveratrol. The inhibition rates for 20 mg/kg or 10 mg/kg 5-FU in combination with 10 mg/kg resveratrol were 77.4% and 72.4%, respectively, compared with the group of 20 mg/kg or 10 mg/kg 5-FU alone, in which the inhibition rates were 53.4% and 43.8%, respectively (n = 8). There was a statistical significance between the combination group and 5-FU group. CONCLUSION: RES could induce the S phase arrest of H22 cells and enhance the anti-tumor effect of 5-FU on murine hepatoma22 and antagonize its toxicity markedly. These results suggest that resveratrol, as a biochemical modulator to enhance the therapeutic effects of 5-FU, may be potentially useful in cancer chemotherapy.     

Endostatin, an antiangiogenic drug, induces tumor stabilization after chemotherapy or anti-CD20 therapy in a NOD/SCID mouse model of human high-grade non-Hodgkin lymphoma

Both chemotherapy and chimeric anti-CD20 monoclonal antibodies are effective agents against B-cell non-Hodgkin lymphoma (NHL). However, patients achieving remission are at risk of relapse. To evaluate the effect of the antiangiogenic drug endostatin used alone and after the administration of cyclophosphamide (CTX) or the anti-CD20 antibody rituximab, we generated a new model of human NHL by transplanting Namalwa cells intraperitoneally into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. First, we determined the most effective treatment schedule for the drugs assessed. When administered alone, CTX (3 courses of 75 mg/kg of body weight given intraperitoneally), rituximab (3 courses of 25 mg/kg given intraperitoneally), and endostatin (5 courses of 50 microg given subcutaneously) delayed tumor growth, and CTX was the most effective in controlling bulky disease. When given after chemotherapy or immunotherapy, endostatin effectively induced tumor stabilization. When mice given CTX or rituximab on days 3, 5, and 7 after transplantation were randomly assigned to receive endostatin or phosphate-buffered saline on days 15 to 19, tumor growth was prevented in endostatin-treated mice as long as the drug was administered. Furthermore, administration of endostatin on days 25 to 29 after tumor regrowth still induced significant tumor regression, whereas CTX and rituximab were not effective. The specific antiangiogenic action of endostatin was confirmed by in vitro and in vivo studies indicating that the drug inhibited proliferation and induced apoptosis of endothelial (but not of NHL) cells. In conclusion, sequential administration of chemotherapy and endostatin seems promising for treating bulky NHL, and the less toxic sequential administration of rituximab and endostatin is promising for treating limited disease. (     

海藻硫酸多糖对肺癌增殖的抑制作用及其机制

目的　探讨海藻硫酸多糖 (SPA)对肺癌增殖的抑制作用及其可能的机制。方法(1)建立Lewis肺癌小鼠模型 ,以抽签法随机分为对照组 ,SPA 2 0、4 0、80mg/kg组及替加氟 (FT 2 0 7)组 ,每组 10只 ,从接种肿瘤次日开始分别灌服生理盐水 ,SPA 2 0、4 0、80mg/kg及FT 2 0 715 0mg/kg ,连续 10d。末次给药后 2 4h处死小鼠 ,剥取肿瘤 ,称瘤重 ,计算抑瘤率。同时应用体外细胞培养模型 ,采用甲基噻唑基四唑 (MTT)法检测SPA在体外对肺癌细胞增殖的影响。 (2 )取雄性新西兰兔 6只 ,按抽签法随机分为对照组、SPA组及环磷酰胺 (CTX)组 ,分别口服生理盐水、SPA 5 0 0mg/kg、CTX 10 0mg/kg,连续10d。最后 1次灌药后 2h ,采集含药血清 ,通过流式细胞仪观察SPA及其含药血清对A5 4 9肺癌细胞增殖、凋亡、细胞周期以及凋亡相关基因p5 3、bcl 2的影响。结果　 (1) 2 0、4 0、80mg/kgSPA连续灌服给药 10d ,对小鼠Lewis肺癌的生长具有明显抑制作用 ,抑制率分别为 35 .2 7%、4 8.2 9%和 6 5 .4 1%。体外SPA在 2 5～ 10 0 μg/ml范围内对A5 4 9肺癌细胞生长无明显抑制作用 (P >0 .0 5 )。 (2 )含SPA兔血清在体外可明显抑制肺癌细胞增殖、诱导癌细胞凋亡 ,出现明显的细胞周期阻滞。A5 4 9细胞株经含SPA兔血清作用后 ,p5 3阳性蛋白标记