Ⅰ-单克隆抗体对人卵巢癌细胞株OC-3-VGH裸鼠皮下移植瘤的抑制作用

目的： 探索131I-单克隆抗体对人OC-3-VGH卵巢癌裸鼠肿瘤的抑制作用。方法：建立人卵巢癌裸鼠皮下移植瘤模型,将28只移植瘤模型裸鼠随机分成7组,即阴性对照组 (等体积生理盐水)、60 mg/kg环磷酰胺 (cyclophosphamide,CP)阳性组、单抗高 (10 mg/kg)、低 (2 mg/kg)剂量组、131I-单抗高剂量组 (10 mg/kg＋125 μCi)、131I-单抗中剂量组 (6 mg/kg＋75 μCi)、131I-单抗低剂量组 (2 mg/kg＋25 μCi),各组连续腹腔给药14 d,分别在第0天 (d0)、d4、d8、d12、d15称量裸鼠体质量,测量肿瘤体积,于末次给药后24 h,剖瘤称取质量,计算相对肿瘤增殖率和抑瘤率。结果：与阴性对照组相比,单抗高剂量组、131I-单抗中、高剂量组均显著抑制肿瘤生长,相对肿瘤增殖率分别是54%、48%、30%,抑瘤率分别为33.59%、45.80%、64.89%,差异均具有统计学意义 (P＜0.01),单抗高剂量组与131I-单抗高剂量组间的差异也具有统计学意义 (P＜0.05)。结论：单克隆抗体和131I-单克隆抗体对人OC-3-VGH卵巢癌均有明显的抑制作用,131I-单克隆抗体高剂量组有明显的增效作用。     

IFN—α仪对人宫颈癌裸鼠皮下移植瘤生长的影响

目的 :研究IFN α对人宫颈癌裸鼠皮下移植瘤生长的影响。方法 :2 8只人宫颈癌裸鼠皮下移植瘤模型随机分为 4组 :对照组 (皮下注射生理盐水 )、顺铂对照组 (腹腔注射 )、IFN α低剂量组 (1 5× 10 7u/kg ,皮下注射 )、IFN α高剂量组 (3 0× 10 7u/kg ,皮下注射 ) ,观察各组移植瘤生长情况 ,裸鼠体重变化 ,计算抑瘤率 ,FCM检测各组移植瘤细胞周期S +G2 M所占比例。结果 :DDP组抑瘤率 92 8% ,IFN α低剂量组抑瘤率为 73 8% ,IFN α高剂量组抑瘤率为 93 1% ,三组分别与对照组 (抑瘤率为 0 % )相比 ,差异均有极显著性 (P <0 0 1) ;IFN α低剂量组与IFN α高剂量组比较 ,差异有极显著性 (P <0 0 1)。FCM检测发现DDP组S +G2 M (31 91%± 4 14 % )低于对照组 (37 76 %± 3 86 % ) ,差异有显著性 (P <0 0 5 ) ,而IFN α低剂量组 (35 4 3%± 7 76 % )和IFN α高剂量组(35 79%± 3 95 % )分别与对照组比较 ,差异无显著性。结论 :IFN α对人宫颈癌裸鼠皮下移植瘤有明显抑制作用 ;剂量效果与抑瘤有关 ;对移植瘤的增殖无明显抑制作用 ,其抑瘤作用可能是通过其他机制。     

蒿甲醚对小鼠结直肠癌的抑瘤及抗血管生成的实验研究

目的:探讨蒿甲醚(Artemether)对BALB/c小鼠CT-26 结直肠癌的抑瘤及抗血管生成作用.方法:BALB/c小鼠皮下接种CT-26 结直肠癌细胞(2×10 6 mL -1)48只,雌、雄各半;随机分为6组,每组8只,分别为低剂量33.3 mg/(kg·d)、中剂量50 mg/(kg·d)、高剂量66.6 mg/(kg·d)和中剂量50 mg/(kg·d)加铁剂1.5 mg/(kg·d)组、阳性对照组为顺铂5 mg/(kg·d)、空白对照组为等体积生理盐水;均在接种5 d后,顺铂采用腹腔注射15 d停药,其余采用灌胃法持续给药15 d,每天1次,末次给药24 h后,处死动物.用Steel公式计算肿瘤体积V(mm 3)=0.5 ab 2.采用免疫组化方法检测移植瘤组织微血管密度.结果:各治疗组抑瘤率分别为42.3%、51.4%、52.0%和53.5%;血管计数分别为13±6、31±4、38±5和11±9,生理盐水对照组为49±9;各治疗组微血管密度均明显低于生理盐水对照组(分别P＜0.05,P＜0.01);移植瘤体积较对照组显著减小.结论:在一定剂量范围内,口服蒿甲醚对小鼠CT-26结直肠癌移植瘤有明显的抑制作用;与铁剂合用能使抑瘤率增加;在具有抑瘤作用的同时,蒿甲醚还具有明显抑制小鼠结直肠癌移植瘤血管生成作用.     

Bcl-XL反义寡核苷酸对裸鼠人食管癌移植瘤抑制作用的研究

目的探讨Bcl-XL反义寡核苷酸(ASODN)对裸鼠体内人食管癌移植瘤的抑制作用.方法建立裸鼠体内人食管癌移植瘤动物模型,当移植瘤平均体积约为50mm3时,在裸鼠体内进行连续15d的Bcl-XL ASODN治疗,观察人食管癌移植瘤的生长情况和组织形态学改变,应用RT-PCR和Western Blot检测肿瘤组织中Bcl-XL mRNA和蛋白表达水平的改变以及凋亡的原位末端标记检测肿瘤的凋亡情况.结果裸鼠体内人食管癌移植瘤的生长受到明显抑制,治疗后,对照组、无关序列寡核苷酸(N-ODN)组和ASODN组的移植瘤体积分别为(1 062.8±599.7)mm3、(853.0±327.9)mm3和(267.7±152.3)mm3,ASODN组与对照组及N-ODN组比较,具有显著性差异(P＜0.05).同时,ASODN组的Bcl-XL mRNA及蛋白表达受到抑制,并且移植瘤组织中凋亡细胞显著增加(P＜0.05).结论Bcl-XLASODN可有效抑制裸鼠体内人食管癌移植瘤的生长,为食管癌的基因治疗提供重要的理论依据.     

半枝莲对结直肠癌裸鼠皮下移植瘤生长的抑制作用及其机制

目的观察半枝莲提取物对人结直肠癌裸鼠皮下移植瘤生长的抑制作用,并探讨其作用机制。方法建立人结直肠癌裸鼠皮下移植瘤模型,将24只小鼠随机分为模型组、5-Fu组(阳性对照)、半枝莲低剂量组和半枝莲高剂量组,观察并记录各组裸鼠移植瘤的生长情况,计算肿瘤抑制率。Western blot和免疫组织化学法检测各组裸鼠皮下移植瘤中TWIST和MMP-2表达水平,并分析其相关性。结果半枝莲高剂量组移植瘤瘤重和体积均较模型组明显减轻或缩小,高剂量组抑瘤率与5-Fu组差异无统计学意义(P>0.05);半枝莲高剂量组移植瘤TWIST和MMP-2的表达较模型组均明显降低(P<0.05),与阳性药5-Fu相当。结论一定剂量的半枝莲对人结直肠癌移植瘤具有明显的抑制作用,其机制可能与抑制TWIST和MMP-2的协同表达有关。     

抗肝癌重组免疫毒素对荷人肝癌裸鼠移植瘤生长的抑制作用

目的:观察二硫键稳定人源化抗肝癌单链抗体(humanized disulfide stabilization single chain antibody,hdsFv)融合牛蛙核糖核酸酶(rana catesbeiana ribonuclease,RC-RNase)重组免疫毒素(hdsFv-RC-RN-ase)对荷人肝癌裸鼠移植瘤生长的抑制作用。方法:将人肝癌细胞系SMMC-7721细胞接种于裸鼠皮下,建立荷人肝癌裸鼠移植瘤动物模型,随机分为3组,分别经尾静脉注射给予生理盐水、盐酸多柔比星和抗肝癌hdsFv-RC-RNase治疗,疗程为2周。通过测量各实验组裸鼠肿瘤体积及瘤质量变化,绘制肿瘤生长曲线并计算抑瘤率。治疗结束后取各组裸鼠肿瘤组织及重要器官HE染色,光学显微镜下观察。结果:治疗后hdsFv-RC-RNase组与空白对照组相比较,荷人肝癌裸鼠移植瘤生长速度显著减慢,肿瘤体积和瘤质量明显减小,P<0·01;同样,与盐酸多柔比星组相比较差异有统计学意义,P<0·01。hdsFv-RC-RNase组和盐酸多柔比星组抑瘤率分别为(78·9±4·1)%和(70·3±6·6)%,P<0·01。光学显微镜下观察hdsFv-RC-RNase组和盐酸多柔比星组肿瘤组织出现明显坏死,尤以前者更为显著。各实验组裸鼠重要器官未见明显异常。结论:抗肝癌hdsFv-RC-RNase重组免疫毒素对荷人肝癌裸鼠移植瘤生长具有良好的抑制作用。     

米非司酮对裸鼠子宫内膜癌细胞HHUA移植瘤生长及COX-2、CDK4的影响

背景与目的子宫内膜癌是女性常见的恶性肿瘤,内膜癌中存在COX-2,CDK4的表达,并与肿瘤的发生发展有关,近年来发现米非司酮有抗肿瘤作用,但其作用机制不十分明了,我们研究米非司酮(mifeprisitone,MIF)对人子宫内膜癌HHUA细胞株裸鼠移植瘤生长的抑制作用及对COX-2,CDK4的影响,以确定米非司酮能否通过干预肿瘤中COX-2,CDK4的表达而抑制肿瘤生长。方法体外培养人子宫内膜癌HHUA细胞,裸鼠皮下接种细胞建立裸鼠移植瘤动物模型,随机将10只移植瘤荷瘤裸鼠分为两组,MIF组采用灌胃法[50mg/(kg·d)],对照组灌等量溶剂。观察治疗前后移植瘤的体积变化。免疫组织化学染色法检测移植瘤组织COX-2、CDK4的表达,后采用Leica IM50免疫组织化学评分软件(HSCORE)对染色结果进行半定量分析,HE染色观察肿瘤组织的病理变化。结果治疗6周后,MIF组移植瘤体积(115.25±10.97)mm3,对照组移植瘤体积(313.25±43.92)mm3,两者相比,差异有非常显著性(P<0.01);HE染色见MIF组较对照组移植瘤坏死面积显著增加;MIF组COX-2HSCOREs为(78.2±11.3),对照组(205.9±26.7),两者相比,差异有显著性(P<0.01);MIF组CDK4HSCOREs为(113.4±18.2),对照组HSCOREs为(238.7±35.9),两者相比,差异有非常显著性(P<0.01)。结论MIF具有抑制人子宫内膜癌细胞HHUA裸鼠移植瘤生长的作用;其机制可能与下调COX-2、CDK4的表达有关。     

Bcl-2反义寡核苷酸对裸鼠人肺癌移植瘤抑制作用的研究

目的探讨Bcl-2反义寡核核苷酸(ASODN)对裸鼠人肺癌移植瘤的成瘤能力和生长的抑制作用。方法将经硫代修饰的Bcl-2ASODN导入非小细胞肺癌。NCI-H460细胞内,然后将这种细胞接种于裸鼠皮下,观察肿瘤出现的时间和肿瘤体积的变化,并计算抑瘤率。同时采用未经处理的NCI-H460细胞接种于裸鼠背部皮下建立裸鼠人肺癌移植瘤模型,待长出瘤结节直径为≥5mm后,分为Bcl-2ASODN实验组、生理盐水对照组和无义寡核苷酸对照组3组。实验组用15mg/kgASODN两天一次直接瘤内注射,连用3周,测肿瘤大小变化和组织形态学改变。结果Bcl-2ASODN作用后的NCI-H460细胞在裸鼠皮下成瘤能力降低,最大抑瘤率达87.5%(P相似文献   

NRP-1单抗联合节律化疗对裸鼠胃癌移植瘤生长的抑制

目的：探讨NRP-1 单抗联合多西他赛节律化疗对胃癌裸鼠移植瘤的抗肿瘤疗效。方法：BALB/c裸鼠皮下接种胃癌BGC-823 细胞制备移植瘤模型,将荷瘤裸鼠以数字随机表法随机分为对照组、NRP-1 单抗组、节律化疗组(MCT)、联合组(NRP-1mAb+MCT),每组6 只。除对照组,其余各组于造模第8 天开始分别给予相应治疗,给药2 周,观察裸鼠一般状况,隔天测量裸鼠体重及肿瘤体积。裸鼠处死后称瘤质量,H-E 染色观察瘤组织形态,免疫组化检测裸鼠瘤组织中NRP-1 蛋白、VEGF、MVD表达。结果：联合组移植瘤的体积和质量显著低于其他各组[ （0.394±0.128）vs（0.748±0.152）、0.867±0.361）、（1.247±0.494）g;（0.613±0.223) vs (0.866±0.115)、(1.098±0.343)、(1.474±0.644) cm3。均P<0.05],抑瘤率较其他治疗组差异有统计学意义(P<0.05)。对照组癌组织细胞生长良好,血管丰富,给药组癌组织出现不同程度的片状坏死,血管成分减少。免疫组化染色显示,对照组NRP-1 表达明显高于治疗各组(P<0.05),联合组的NRP-1、VEGF、MVD表达均显著低于其余各组(P<0.05)。结论：NRP-1单抗联合多西他赛节律化疗可能通过下调NRP-1 表达而显著抑制BGC-823 胃癌移植瘤的生长及血管生成。     

125I放射性粒子对人食管癌裸鼠皮下移植瘤的抑制作用研究

目的:观察125I粒子植入对人食管癌裸鼠皮下移植瘤的抑制作用.方法:采用雄性BALB/C裸小鼠建立人食管癌Eca-109细胞株的裸鼠皮下移植瘤模型,将荷瘤鼠随机分为5组(每组5只):对照组(A组)、假手术组(B组) 、低剂量组(C组,植入7.4 ×106 Bq粒子1枚)、中剂量组(D组,植入14.8 ×106 Bq粒子1枚)和高剂量组(E组,植入29.6 ×106 Bq粒子1枚).第30天检测各组移植瘤体积,并观察各组移植瘤组织病理学变化.结果: C、D、E组瘤体积与A组比较显著缩小,差异均有统计学意义(P<0.05), D、E组瘤体积与C组瘤体积相比均有统计学意义(均P<0.05),但D、E组之间瘤体积相比差异无统计学意义(P>0.05).B组和A组瘤体积相比差异无统计学意义(P>0.05),C、D、E植入后30d肿瘤体积抑瘤率分别为71.5 %、90.8%、92.1%. 结论:125I粒子对人食管癌裸鼠移植瘤具有一定的抑制和杀伤作用.     

Combining radioimmunotherapy and chemotherapy for treatment of medullary thyroid carcinoma: effectiveness of dacarbazine

BACKGROUND: To enhance the efficacy of chemotherapy for medullary thyroid carcinoma (MTC), we evaluated the effect of combining radioimmunotherapy (RAIT) with 90Y-anticarcinoembryonic antigen (CEA) monoclonal antibody MN-14 and chemotherapy in nude mice bearing human MTC xenografts. A preliminary study evaluated doxorubicin, dacarbazine (DTIC), cyclophosphamide, and vincristine, singly and in combination, for their effect on the growth of MTC xenografts (TT) in nude mice. Given individually, DTIC yielded the most effective tumor growth inhibition, delaying the mean time to doubling from 1 week for untreated tumor-bearing mice to 7.5 weeks. Administering either the 4 drugs in combination or a 2-drug combination comprised of doxorubicin and DTIC significantly improved the efficacy compared with any single drug alone, increasing the mean doubling time to 10-12 weeks. METHODS: Drug doses were selected to conform to the doses of each drug given clinically. For the combined modality therapy, administration of 90Y-labeled anti-CEA monoclonal antibody MN-14 to nude mice bearing established TT tumors was followed by various chemotherapy regimens initiated 24 hours after RAIT. Chemotherapy protocols combined with RAIT included doxorubicin or DTIC alone and in combination, and the doxorubicin, DTIC, cyclophosphamide, and vincristine 4-drug protocol. Tumor volumes were measured weekly, and toxicity was evaluated by measuring blood counts and body weight. RESULTS: Combinations of RAIT and chemotherapy with DTIC or RAIT and chemotherapy with the drug combinations were found to augment the antitumor effects of RAIT or chemotherapy alone, without a significant increase in toxicity. The mean tumor volume doubling times were increased up to 100% compared with the results of chemotherapy alone. No significant differences in tumor growth were observed between the RAIT plus DTIC protocol and the RAIT plus two- or four-drug protocols. CONCLUSIONS: The superiority of the combined modality treatment argues for the integration of RAIT into chemotherapeutic regimens for MTC treatment. Clinical trials are needed to assess these principles in MTC patients.     

Colonic tumor CEA, CSAp and MUC-1 expression following radioimmunotherapy or chemotherapy.

Understanding the changes in tumor biology following cytotoxic therapy may lead to a better understanding of the properties of surviving tumor cell populations and to an improved ability to target and treat these cells. This report addressed the time-dependent dynamic alterations in the expression of three tumor-associated antigens: carcinoembryonic antigen (CEA), colon-specific antigen (CSAp) and mucin-1 (MUC-1) following chemotherapy with 5-fluorouracil (5-FU) or radioimmunotherapy (RAIT; (131)I-labeled anti-CEA IgG) in human colonic tumor xenografts. Immunoassay results show that CEA and MUC-1 expression all increase rapidly after either 5-FU or RAIT. GW-39 tumors show a 2.7-fold increase in CEA expression after a maximum tolerated dose of RAIT, being highest after 21 days, while LS174T and HT-29 tumors maximally increase expression 8.3- and 2.6-fold on day 7 after RAIT, respectively. The change in LS174T is short-term, whereas the change in HT-29 is maintained for at least 4 weeks. Serum CEA levels in these tumor- bearing mice also increase in parallel to the changes observed in tumor. MUC-1 increases 2.5-fold by day 5-7 following RAIT in LS174T tumors and 6-fold by day 14 following RAIT in GW-39 tumors, with a corresponding increase in serum MUC-1. Dramatic increases in CSAp after RAIT were also demonstrated in GW-39 tissue by immunohistochemistry. Thus, these data indicate that the response of tumor cells to low-dose-rate radiation from RAIT or to chemotherapy is associated with an increase of CEA, MUC-1 and CSAp.     

Effect of the selective estrogen receptor modulator arzoxifene on repopulation of hormone-responsive breast cancer xenografts between courses of chemotherapy.

Selective inhibition of repopulation of clonogenic tumor cells between courses of chemotherapy has potential to improve the effectiveness of treatment. Here we study arzoxifene, a short-acting selective estrogen receptor modulator, for its potential to inhibit repopulation in estrogen-dependent human breast cancer MCF-7 xenografts between courses of chemotherapy. Proliferation of tumor cells was evaluated by cyclin D1 expression and uptake of 5-bromo-2'-deoxyuridine. Arzoxifene decreased cell proliferation in xenografts. To model adjuvant treatment of human breast cancer, MCF-7 cells were injected s.c. into nude mice and four groups of mice received the following treatments beginning after implantation: (a) control (vehicle solution); (b) arzoxifene alone, 5 days per week by oral gavage for 3 weeks; (c) 5-fluorouracil (5-FU) or paclitaxel i.p. weekly, for 3 doses; and (d) arzoxifene following each cycle of chemotherapy. The incidence of tumors with volume > or =50 mm(3) was determined as a function of time. MCF-7 xenografts developed in 100% of control mice by 4 weeks after implantation. Paclitaxel or 5-FU alone had minor effects to delay the appearance of xenografts whereas arzoxifene alone caused longer delay. Combined treatment with arzoxifene given between cycles of 5-FU or paclitaxel had substantial effects, with approximately 50% tumor incidence by 5 weeks. Our results indicate that arzoxifene can inhibit repopulation of hormone-responsive MCF-7 breast cancer xenografts when given between courses of chemotherapy. The scheduling of short-acting hormonal agents between courses of adjuvant chemotherapy for human breast cancer has potential to improve the outcome of treatment.     

Anti-oxidant vitamins reduce normal tissue toxicity induced by radio-immunotherapy

Our purpose was to determine whether the administration of anti-oxidant vitamins could reduce dose-limiting toxicity from radio-immunotherapy (RAIT) and thereby allow higher escalation of RAIT doses. Lipophilic vitamins A and E were administered i.p. and hydrophilic vitamin C was administered i.m. for 14 days (3 days pre-RAIT through 11 days post-RAIT) alone or with bone marrow transplantation (BMT) to either BALB/c mice for toxicity studies or to nude mice bearing s.c. GW-39 human colonic cancer xenografts for therapy studies. The maximal tolerated dose (MTD) of RAIT ((131)I-MN14 anti-CEA IgG) that results in no lethality was determined for mice that did not receive vitamins or BMT and those that did receive one or both interventions. Body weight, peripheral white blood cell (pWBC) and platelet (PLT) counts and tumor growth were also measured. Administration of vitamins (equivalent of 3.5 IU/day vitamin A, 0.107 IU/day vitamin E and 4.0 mg/day ascorbic acid) to mice along with BMT increased the MTD by 42% and reduced body weight loss associated with RAIT. Vitamins also reduced the magnitude of RAIT-induced myelosuppression. As early as day 7 after RAIT, vitamins increased WBC counts following both a 400 microCi and a 500 microCi dose. On day 14 after the 400 microCi dose of RAIT (day 7 post-BMT), the additive effect of BMT and vitamin could be detected. Tumor growth was not adversely affected by vitamin administration.     

Targeting study of human hepatocellular carcinoma (HCC) using human HCC model in nude mice

Fifty-three nude mice bearing human HCC were used for targeting study of HCC using 131I-antihuman HCC isoferritin IgG. Of these mice, 17 were used for radioimaging with 131I-labeled IgG, 131I-labeled albumin and 131NaI. In labeled IgG group, all tumors were positively visualized by gamma camera with the best imaging on the 7th day after injection of labeled IgG (200 microCi, ip), the tumor/liver radioactivity ratio being 2.7. The dose of tumor radioactivity at the 7th day was 7-10 times higher than that in labeled albumin group. Thirty-six mice were used for the study of radioimmunotherapy with 131I-labeled IgG, 131NaI and IgG (n = 9, 300 microCi/50 micrograms, ip). The tumor inhibition rate in the labeled IgG group at 4th week after treatment was significantly higher than those of the other groups (81%, 60% and 18%, respectively, P less than 0.05). Tumor cell DNA analysis showed that the tumor cells were inhibited in S stage of the cell cycle. In the same way, five kinds of substances with affinity to HCC were studied in this animal model. The result indicates that the transplantable nude mice-human HCC model is acceptable for targeting study of HCC.     

Experimental studies on subrenal capsule assay using cyclosporin A treated mice--the optimal treatment schedules of CsA and anticancer agents (mitomycin C and 5-fluorouracil)

We studied fundamentally subrenal capsule assay, using human tumor specimens (breast, gastric and colon cancers) serially transplanted in nude mice. When cancer anticancer agents such as mitomycin C (MMC) and 5-fluorouracil (5-FU) were injected into immunocompetent mice treated with various dosages of cyclosporin A (CsA) after tumor implantation, optimal schedule of each drug was examined on the points of effects and toxicity against host mice. The following results were obtained. Control groups were set up as immunocompetent mice which treated daily with 60 mg/kg CsA from day 1 after tumor implantation. Optimal treatment schedule was judged as MMC 3 mg/kg i.v. injection on day 1 following by daily 60 mg/kg CsA treatment, and 5-FU was injected 25 mg/kg subcutaneous injection every day from day 1 without CsA treatment, each schedule showed an appropriate anti-tumor activity profiles against implanted tumor xenografts, and had less toxicity to the hosts.     

Radioimmunotherapy of human colon cancer xenografts by using 131I labeled-CAb1 F(ab')2

PURPOSE: Therapeutic efficacy, suitable dose, and administration times of 131I-CAb1 F(ab')2, a new monoclonal antibody therapeutics specifically directed against a cell surface-associated glycoprotein of colon cancer, were investigated in this article. METHODS AND MATERIALS: In human colon cancer xenografts, 131I-CAb1 F(ab')2 at the dose of 125 muCi, 375 muCi, and 1125 muCi were administrated intraperitoneally on Days 6 and 18 after implantation of HR8348 cells with CAb1 high reactivity. Survival time and tumor growth inhibition rate were used to evaluate the efficacy and safety of 131I-CAb1 F(ab')2 in treatment of colon cancer xenografts. RESULTS: Treatment of 125, 375, and 1125 muCi 131I-CAb1 F(ab')2 did not significantly decrease the mean survival time of nude mice when compared with nontreated groups (p = 0.276, 0.865, 0.582, respectively). Moreover, the mean survival times of nude mice receiving 375 muCi and 1125 muCi 131I-CAb1 F(ab')2 were significantly longer than that of 5-FU-treated groups (p = 0.018 and 0.042). Tumor growth inhibition rates of the first therapy were 35.67% and 41.37%, with corresponding 131I-labeled antibody dosage of 375 muCi and 1125 muCi. After single attack dosage, second reinforcement therapy may rise efficacy significantly. Tumor growth inhibition rates of 125 muCi, 375 muCi, and 1125 muCi 131I-labeled antibody on Day 20 posttherapy were 42.65%, 56.56%, and 84.41%, respectively. Histopathology examination revealed that tissue necrosis of various degrees was found in 131I-CAb1 F(ab')2-treated groups. CONCLUSION: 131I-CAb1 F(ab')2 is safe and effective for colon cancer. It may be a novel and potentially adjuvant therapeutics for colon cancer.     

Cyclooxygenase inhibitors decrease the growth and induce regression of human esophageal adenocarcinoma xenografts in nude mice

Cyclooxygenase (COX) inhibition has been shown to prevent the development of esophageal adenocarcinoma (EAC). However, the potential of this approach for treatment of established cancer has been poorly investigated. Our objective was to determine whether non-selective or selective inhibition of the COX pathway affects the growth of esophageal adenocarcinoma xenografts in nude mice. A human esophageal adenocarcinoma xenograft model was established by subcutaneous inoculation of OE33 cells in nude mice. Small tumor slices harvested from four OE33 xenografts were implanted in the flanks of new mice that were randomized to different treatments (6 animals per group): indomethacin (3 mg/kg/day), parecoxib (0.11 and 0.22 mg/kg/day) or a selective prostaglandin E? receptor antagonist (AH-23848B, 1 mg/kg/day). For each treatment, a control group of 6 animals (vehicle) carrying xenografts from the same OE33 tumor was included. Tumor growth was measured twice a week. After 8 weeks mice were euthanized. Tumors were assessed by histological analysis, mRNA expression of COX isoenzymes, PGE? receptors and PGE? content. All OE33 tumors were poorly differentiated esophageal adenocarcinomas. Tumors expressed COX-2, EP?, EP? and EP? receptor mRNA. Treatment with parecoxib, higher dose or indomethacin significantly inhibited tumor growth. Furthermore, indomethacin induced tumor regression (74 vs 582% in control animals; p<0.01). However, AH-23848B or parecoxib low dose failed to affect tumor growth significantly. PGE? content in tumors was significantly decreased by high-dose parecoxib and indomethacin. Indomethacin and parecoxib inhibit the growth of human esophageal adenocarcinoma xenografts in nude mice, which suggests a potential role for NSAIDs or selective COX-2 inhibitors for EAC chemotherapy.     

Effect of cholecystokinin on human cholangiocarcinoma xenografted into nude mice

Gastrointestinal polypeptide hormones regulate growth of various normal gastrointestinal tissues as well as certain visceral cancers. Since cholecystokinin (CCK) promotes growth of normal biliary tract, we sought to determine whether CCK affects the growth and metabolism of human cholangiocarcinoma line SLU 132. Twenty-six nude mice with s.c. xenografts of this cancer received either CCK octapeptide (50 micrograms/kg/dose) or 0.9% NaCl solution (saline) twice a day i.p. for 14 days. Tumor volume was calculated from Vernier caliper measurements. At sacrifice on Day 15, tumors were excised, weighed, and examined histologically. DNA, RNA, and protein were measured in the xenografted carcinomas. Because this cholangiocarcinoma produces carcinoembryonic antigen (CEA), we obtained serum at sacrifice for CEA radioimmunoassay and also tumor tissue for CEA immunolabeling with murine anti-CEA monoclonal antibody. Serum CEA levels were 90% higher in the CCK-treated group. Tumor tissue in the CCK-treated group also contained more CEA than did the controls. Mean tumor volume increased significantly in the saline group during the 14-day treatment period, whereas mean tumor volume did not increase significantly in the CCK group. Exogenous high-dose CCK thus appears to increase production and release of CEA from SLU-132; it also appears to retard growth of this tumor line in the nude mouse.     

小剂量放射免疫治疗的可行性及安全性的实验研究

目的　研究多次小剂量放射免疫治疗 (RIT )对肿瘤小体积转移灶的预防和治疗作用及使用安全性。方法　采用高转移率的LA 795肺腺癌小鼠模型。比较在第 8天或第 15天施行肿瘤原发灶切除后分别给予分次小剂量RIT、化疗、单次大剂量RIT的抑瘤效果。观察正常小鼠放射免疫治疗后体重、外周血白细胞和血小板的改变及主要器官组织病理改变。结果　不同手术时间的综合治疗均显示 ,分次小剂量RIT组小鼠生存期延长 ,肺转移灶数减少 (分别有 3例和 2例无转移 ) ,疗效优于其它各组 (P<0 .0 5 )。提早手术并分次小剂量放射免疫治疗的疗效更佳 (P <0 .0 5 )。大、小 2种剂量131I C5 0对小鼠的白细胞、血小板的数量无显著影响 ;对骨髓及其它重要器官无明显的抑制和辐射损伤。结论　分次小剂量RIT优于化疗 ;提前手术加分次小剂量RIT疗效更优 ;131I C5 0小剂量放射免疫治疗是安全的。