~(131)抗CEA单抗治疗结肠腺癌肝转移裸鼠对CEA水平影响的研究

目的　探索应用1 31 I标记抗CEA单抗治疗结肠腺癌肝转移后对荷瘤裸鼠血清、腹水和癌组织中CEA水平的影响。方法　在建立人结肠腺癌裸鼠肝转移后 10min(早期治疗组 )、10d(中期治疗组 )、2 0d(晚期治疗组 )经尾静脉注射1 31 I标记抗CEA单抗 ;并以模型建立后经尾静脉注射1 31 I标记的正常小鼠IgG作为对照组。于接种癌细胞 4周后 ,采集血、腹水和癌结节 ,分别检测其CEA含量。结果　早期治疗组的血、腹水和癌结节中CEA水平均明显低于对照组 (P <0 .0 1) ;早期治疗组与晚期治疗组则无显著性差异 (P >0 .0 5 )。结论　早期应用1 31 I标记抗CEA单抗能有效地降低荷瘤裸鼠的血清、腹水和癌结节中CEA水平     

三氧化二砷对人结肠腺癌裸鼠肝转移癌胚抗原水平的影响

目的：探索应用三氧化二砷（As2O3）治疗人结肠腺癌肝转移后对荷瘤裸鼠血清、腹水及癌组织中癌胚抗原（carcinoembryonic，CEA）水平的影响。方法：在建立人结肠腺癌裸鼠肝转移模型后15min（早期治疗组）、10d（中期治疗组）、20d（晚期治疗组）经尾静脉注射As2O3（5mg／kg·d）；并以模型建立后10d经尾静脉注射生理盐水作为对照组。于接种癌细胞4周后，采集血、腹水和癌结节，分别检测其CEA含量。结果：早期治疗组的血、腹水和癌结节中的CEA含量均明显低于对照组（P〈0．01）；晚期治疗组与对照组差异无统计学意义（P〉0．05）。结论：早期应用As2O3能有效刚氐荷瘤裸鼠的血清、腹水和癌结节中CEA水平。     

^131I标记单克隆抗体CL3瘤内注射对荷人结肠癌裸鼠的放射…

我们采用＾１３１Ｉ标记单克隆抗体ＣＬ３瘤内注射治疗荷人结肠癌裸鼠移植瘤，与腹腔注射比较：大剂量组每鼠给药１８．５ＭＢｑ，观察３４天，１６天后前者的肿瘤生长抑制率高于手者，分别为５７．９％±１０．２％和４７．２％±１６．６％（Ｐ＜０．０５），肿瘤完全抑制率分别为６／１６和１／８；小剂量组每例５．３６ＭＢｑ观察１７天，６天后，前者的肿瘤生长抑制率明显高于后者，分别为４９．６％±１７．５％和２６．１％±     

^131I—抗膀胱癌单克隆抗体对荷瘤裸鼠的放射免疫治疗研究

用＾１３１Ｉ标记的抗ＢＩＵ－８７ＭｃＡｂ对荷人膀胱癌裸鼠进行放射免疫治疗，结果显示对肿瘤对明显的抑制作用。高剂量组（１４８００ｋＢｑ组）疗效明显优于低剂量组（７４００ｋＢｑ组），其治疗后第４周对肿瘤的抑制率分别为９９％及７２％。未发现１４８００ｋＢｑ＾１３１Ｉ－抗ＢＩＵ－８７ＭｃＡｂ对小鼠产生毒性。     

131 I标记的抗癌胚抗原抗体C50治疗裸鼠结直肠癌移植瘤的疗效观察

目的　探讨结直肠癌放射免疫治疗 (RAIT)不同治疗剂量用法与疗效的关系。方法建立表达癌胚抗原 (CEA)的人结直肠癌荷瘤裸鼠模型。接种肿瘤细胞第 9天 ,Ⅰ、Ⅱ和Ⅲ组分别尾静脉注射 5 .5 5× 10 6 、7.40× 10 6 、1.11× 10 7Bq的1 3 1 I标记的抗CEA单克隆抗体C5 0 ( 1 3 1 I C5 0 ) ,Ⅳ组分 2次给予总量 1.11× 10 7Bq的1 3 1 I C5 0 ,计算各组裸鼠肿瘤体积、群体倍增时间及抑瘤率 ,比较接种第 30天肿瘤体积。接种第 15天 ,观察肿瘤组织病理学改变。结果　Ⅰ、Ⅱ、Ⅲ和Ⅳ组两两之间接种第 30天肿瘤体积差异均有非常显著性 (P <0 .0 0 1) ,群体倍增时间依次延长 ,抑瘤率依次增大。光学显微镜下见各治疗组肿瘤组织均有不同程度灶状坏死。结论　结直肠癌RAIT疗效呈剂量依赖性。在总治疗剂量相等的情况下 ,分次RAIT疗效优于单次RAIT。     

131Ⅰ标记单克隆抗体CL3瘤内注射对荷人结肠癌裸鼠的放射免疫治疗

我们采用１３１Ⅰ标记单克隆抗体ＣＬ３瘤内注射治疗荷人结肠癌裸鼠移植瘤，与腹腔注射比较：大剂量组每鼠给药１８．５ＭＢｑ，观察３４天，１６天后前者的肿瘤生长抑制率高于后者，分别为５７．９％±１０．２％和４７．２％±１６．６％（Ｐ＜０．０５），肿瘤完全抑制率分别为６／１６和１／８；小剂量组每例５．３６ＭＢｑ，观察１７天，６天后，前者的肿瘤生长抑制率明显高于后者，分别为４９．６％±１７．５％和２６．１％±３．４％（Ｐ＜０．０１）．计算小剂量给药后五天的肿瘤累积吸收剂量，瘤内注射是腹腔注射组的３．３倍，分别为１８．７Ｇｙ和５．７Ｇｙ．结果提示在肿瘤放射免疫治疗中采用瘤内注射法给药，具有低毒高效的治疗作用，临床实用价值较高。     

在结肠腺癌中MicroRNA的表达方式与其预后和治疗效果的相关性

Schetter AJ，Leung SY，Sohn JJ等人通过对MicroRNA（微RNA）的研究来探讨微RNA表达模式与结肠腺癌及其预后和治疗效果的相关性。其试验组中所选的5种微RNA指标在肿瘤组织中均有充分表达（P〈0．001）。原位杂交证明了在结肠癌细胞中miR-21有更高水平的表达。在试验组和验证组中，发现miR-21高表达率的相关因素。     

结肠腺癌中微小RNA-134-5p的表达及与肝转移的关系

目的:检测结肠腺癌中微小RNA(microRNA,miR)-134-5p的表达,分析其与细胞增殖的关联性,探讨其与肝转移的关系。方法:2013年4月至2014年8月,收集大连大学附属中山医院确诊为结肠腺癌并行手术治疗的患者共69例作为研究对象,选取肿瘤组织作为观察组,选取距肿瘤的边缘>5 cm的正常结肠组织作为对照组。...     

经门静脉注射131I标记抗癌胚抗原单克隆抗体预防人结肠腺癌肝转移的实验研究

我们进行了经门静脉注射13 1Ｉ标记抗癌胚抗原(13 1Ｉ ＣＥＡ)单克隆抗体预防人结肠腺癌肝转移的实验研究 ,报告如下。材料与方法1.人源性结肠癌裸鼠肝转移模型 :4～ 6周龄的ＢＡＬＢ/Ｃｎｕ/ｎｕ裸鼠 (第三军医大学实验动物所提供 ) ,雌雄兼用 ,体重17～ 2 5ｇ ,在无致病菌 (ＳＰＦ)条件中饲养。按左国华和葛海燕[1] 方法制作结肠癌肝转移模型。2 .采用Ｉｏｄｏｇｅｎ固相法碘化标记鼠抗人ＣＥＡ单克隆抗体ＣＯＬ 1[2 ] 。3.实验分组 :将 30只裸鼠随机分成Ａ、Ｂ、Ｃ 3组 ,每组 10只。在脾内注射癌细胞后 10ｍｉｎ ,Ａ组经脾脏注射 11 1Ｍ…     

Radioimmunotherapy of human colon cancer in nude mice

Nude mice bearing subcutaneous human colon cancer xenografts (LS174T) were treated with 120 microCi of yttrium 90-labeled anti-carcinoembryonic antigen monoclonal antibodies (specific therapy), 120 microCi of 90Y-labeled anti-melanoma monoclonal antibodies (nonspecific therapy), or phosphate-buffered saline solution (no treatment control). Mean (+/- SD) tumor growth rates (percent increase per day) over the first 30 days of the study were as follows: 0.6% +/- 0.2% per day (specific therapy); 17.7% +/- 5.7% per day (nonspecific therapy); and 30.5% +/- 4.2% per day (control). In all three groups, tumors over 1 g had similar doubling times (5.74 +/- 0.71 d). Specific therapy caused a lag in tumor growth corresponding to a 3-logarithm cell kill. Estimated tumor dose of radiation obtained by tissue analysis was 34 and 14 Gy for specific and nonspecific therapy, respectively. In conclusion, 120 microCi of 90Y-labeled anti-carcinoembryonic antigen monoclonal antibodies was effective in suppressing growth of human colon cancer xenografts. Clinical studies with this preparation are recommended.     

结直肠癌肝转移的诊断和治疗

目的 探讨结直肠癌肝转移的诊断和治疗效果.方法 回顾性分析25 例结直肠癌肝转移的临床资料,其中原发盲升结肠癌9 例,横结肠癌3 例,降结肠癌2 例,乙状结肠癌8 例,直肠癌3 例.同时性肝转移癌9例,异时性肝转移癌16 例.肝左叶转移15 例,肝右叶转移4 例,左右叶转移6 例.单个转移15 例,多个转移10例.高分化腺癌13 例,中分化腺癌5 例,低分化腺癌6 例,未分化腺癌1 例.9 例同时性肝转移癌中施行肝左外叶切除7 例,其中加1 例门静脉插管埋泵化疗;右前叶切除2 例,1 例仅作门静脉和肝动脉双插管埋泵化疗.16例异时性肝转移癌中施行肝左外叶切除4 例,左半肝切除5 例,肝右前叶切除2 例,门静脉和肝动脉双插管埋泵化疗2 例,股动脉插管肝动脉介入治疗3 例.结果 全组均经3 年随访,同时性肝切除术8 例中5 例存活(62.5%),异时性肝切除术11 例中4 例存活(36.3%),仅作门静脉和肝动脉插管埋泵化疗或股动脉插管肝动脉介入化疗6 例中2 年内死亡5 例,3 年死亡1 例,3 年存活率仅16.6%.结论 同时性或异时性结直肠癌肝转移,只要全身情况和局部条件许可,均应首选手术切除治疗,以提高患者生存率.对不能切除的患者,可采用动、静脉插管埋泵或作股动脉插管肝动脉介入化疗,以延长患者生命.     

Relationship between colorectal liver metastases and CEA levels in gallbladder bile.

While computerized tomographic (CT) scanning and intraoperative exploration are both considered accurate measures of liver involvement with metastatic disease, 10% to 30% of colorectal liver metastases remain undetected. Attempting to improve current methods for detecting colorectal liver metastases, CEA levels in gallbladder bile and serum from patients with known liver metastases were determined. One hundred per cent of patients with single and multiple metastases of various dimensions were observed to have gallbladder bile CEA levels strikingly higher than serum values (4.7 to 259 times greater, p = 0.0009). Linear regression analysis of estimated tumor volume and surface area versus gallbladder bile CEA levels predicted that very small tumors (less than or equal to 1 cm3 in volume) might produce detectable levels (9 to 41 ng/mL) of biliary CEA. For this reason, patients who lack clinical and radiologic evidence of distant metastases at the time of primary colorectal resection but who do have elevated gallbladder bile CEA levels (greater than or equal to 10 ng/mL) are being followed for the appearance of occult hepatic metastases.     

结肠癌同时性肝转移同期手术与分期手术的疗效比较

目的：对比结肠癌同时性肝转移行同期手术与分期手术切除转移灶的疗效。方法：回顾性分析36例结肠癌同时性肝转移患者的临床资料,其中16例行结肠癌根治术同时切除肝转移病灶（同期手术组）;20例先行结肠癌根治性切除、二期行肝转移病灶切除（分期手术组）。比较两组患者的1,3,5年生存率。结果：同期手术组患者1,3,5年生存率分别为87.5%,37.5%,18.8%,分期手术组患者1,3,5年生存率分别为65%,10.0%,0.0%。两组比较,1年生存率差异无统计学意义（P>0.05）,同期手术组3,5年生存率明显高于分期手术组（均P<0.05）。结论：结肠癌同时性肝转移行同期手术可延长患者生存时间。

     

原位基因治疗联合前药热化疗治疗结肠癌肝转移的实验研究

目的:探讨胞嘧啶睨氨酶(CD)基因联合5-氟胞嘧啶(5-FC)热化疗对裸鼠结肠癌肝转移的治疗效果.方法:30只BALB/c裸鼠经门静脉注射人结肠癌Lovo细胞建立结肠癌肝转移模型,随机分为转基因组和非转基因组,每组15只.转基因组:经腹腔注射病毒上清(0.2 mL/d,共5d)进行原位基因转染;非转基因组经蝮腔注射生理盐水(0.2 mL/d,共5d),2组同时腹腔注射42℃500 mg·kg-1·d-1)5-FC.治疗21 d后将动物处死,观察肝脏转移率和转移结节数,PCR法检测目的基因在肿瘤组织的整合,RT-PCR法检测目的基因在肿瘤组织的表达,观察肿瘤病理学变化.结果:目的基因成功转染并在肿瘤组织中有效表达.转基因组与非转移基因组肝脏转移率分别为26.7%(4/15)、100.O%(15/15),2组比较差异有统计学意义(P<0.05),肝脏转移结节数分别为0.60±0.83、2.40±0.99(P<0.001).镜下转基因组肝内转移癌细胞变性,染色体消失,可见凋亡小体,而非转基因组未见明显变化.结论:原位基因治疗联合前药热化疗对裸鼠结肠癌肝转移有明显抑制作用.     

Serum CEA levels in patients with gastric carcinoma correlate with the tumorigenicity of their xenografts in nude mice

We examined the correlation among preoperative serum carcinoembryonic antigen (CEA) levels, staining properties of the tumors by CEA immunohistochemistry and the tumorigenicity of their xenografts in nude mice, in 28 patients with gastric cancer. Eleven (40 per cent) of them were positive for serum CEA (greater than or equal to 2.5 ng/ml) and seven (25 per cent) of the xenografts were tumorigenic in nude mice. All the tumorigenic cases were positive for serum CEA (p less than 0.001) and the mean value of the serum CEA level in the patients with tumorigenic neoplasms was 20.8 ng/ml, being significantly higher than that (1.4 ng/ml) in the patients with non-tumorigenic neoplasms (p less than 0.001). Twenty-five of the 28 carcinomas (89 per cent) were positive for CEA staining in their cancer cells by the ABC method and CEA localization correlated with tumorigenicity (p less than 0.05). These results suggest that the serum CEA level in patients is correlated with the tumorigenicity of their gastric carcinoma xenografts in nude mice and may account for the poor prognosis of patients with high serum CEA.     

Serum CEA levels in patients with gastric carcinoma correlate with the tumorigenicity of their xenografts in nude mice

We examined the correlation among preoperative serum carcinoembryonic antigen (CEA) levels, staining properties of the tumors by CEA immunohistochemistry and the tumorigenicity of their xenografts in nude mice, in 28 patients with gastric cancer. Eleven (40 per cent) of them were positive for serum CEA (≧2.5 ng/ml) and seven (25 per cent) of the xenografts were tumorigenic in nude mice. All the tumorigenic cases were positive for serum CEA (p<0.001) and the mean value of the serum CEA level in the patients with tumorigenic neoplasms was 20.8 ng/ml, being significantly higher than that (1.4 ng/ml) in the patients with nontumorigenic neoplasms (p<0.001). Twenty-five of the 28 carcinomas (89 per cent) were positive for CEA staining in their cancer cells by the ABC method and CEA localization correlated with tumorigencity (p<0.05). These results suggest that the serum CEA level in patients is correlated with the tumorigenicity of their gastric carcinoma xenografts in nude mice and may account for the poor prognosis of patients with high serum CEA.     

Vitamin E succinate inhibits colon cancer liver metastases

BACKGROUND: Vitamin E succinate (VES) is a promising anti-cancer micronutrient. In this study, we tested the hypothesis that VES will promote colon cancer tumor dormancy and inhibit liver metastases in colon cancer. METHODS: CT-26 colon cancer cells were treated with VES in vitro and in an in vivo model of liver metastases. The impact of VES on cellular proliferation and apoptosis was measured in vitro by MTS assay and sandwich ELISA and in vivo by PCNA staining and TUNEL assay, respectively. Correlation coefficients and independent t tests were used for statistical analysis. RESULTS: VES significantly and specifically inhibited cell proliferation (P = 0.011) and promoted apoptosis (P < 0.0074) of cancer cells in vitro. VES produced a 40% reduction of liver metastases (P = 0.037). Five of the eight mice had an excellent response to VES. Subsequent analysis of these five mice revealed a 75% reduction in the number of liver metastases (P < 0.05). VES significantly promoted tumor cell apoptosis (P < 0.0003) and inhibited cell proliferation (P = 0.0069) in vivo. CONCLUSIONS: VES inhibits the growth of colon cancer cells in vitro and in vivo. This is the first report of VES inhibition of colon cancer tumor metastases. The mechanism of VES anti-tumor and anti-metastatic activity in vivo appears to involve promotion of tumor apoptosis and inhibition of cell proliferation. These findings support further investigation of VES as a micronutrient to promote colon cancer tumor dormancy and prevent metastases.