白杨素抑制人膀胱癌裸鼠移植瘤生长的初步研究

目的探讨白杨素(Ch R)对膀胱癌T24细胞裸鼠移植瘤生长的影响。方法建立人膀胱癌T24裸鼠皮下异体移植模型(n=40)。接种4周全部成瘤后,将动物随机分为5组:对照组(n=8):腹腔内注射生理盐水,隔日给药1次;丝裂霉素(MMC)组(n=8):腹腔内注射MMC,4 mg/kg,隔日给药1次;低剂量Ch R组(L-Ch R,n=8):腹腔内注射Ch R,20 mg/kg,隔日给药1次;中剂量Ch R组(M-Ch R,n=8):腹腔内注射Ch R,40 mg/kg,隔日给药1次;高剂量Ch R组(H-Ch R,n=8):腹腔内注射Ch R,80 mg/kg,隔日给药1次。连续治疗20 d,裸鼠每周称重2次,测量肿瘤2次,治疗结束处死动物,取出肿瘤称重计算抑瘤率。结果 Ch R(20 mg/kg、40 mg/kg、80 mg/kg)对人膀胱癌T24细胞皮下移植瘤瘤重抑制率分别是40.5%、62.8%和73.4%,与对照组比较,移植瘤重量显著降低(P0.05);不同剂量Ch R组裸鼠的白细胞计数、血清谷丙谷草转氨酶、尿素氮及肌酐与生理盐水模型对照组相比无显著性差异(P0.05)。结论 Ch R能显著抑制人膀胱癌裸鼠移植瘤生长,呈剂量和时间依赖性,是一种毒副作用较小的治疗膀胱癌新候选药物。     

RGD肽联合丝裂霉素C对荷人膀胱癌T24裸鼠肿瘤生长的抑制作用

目的:探讨纤维连接蛋白(FN)拮抗剂精氨酸-甘氨酸-天冬氨酸三肽(RGD)联合丝裂霉素C(MMC)对荷膀胱癌T24裸鼠肿瘤生长的抑制作用。方法:建立荷膀胱癌T24裸鼠模型(n=32)。全部成瘤后随机分为4组:对照组(n=8):瘤体局部注射生理盐水,1次/3d;RGD组(n=8):瘤体局部注射RGD6μg/g,1次/3d;MMC组(n=8):瘤体局部注射MMC2μg/g,1次/3d;RGD MMC组(n=8):瘤体局部注射RGD6μg/g和MMC2μg/g,1次/3d。连续治疗5周后处死动物,取出肿瘤称重,计算抑瘤率。结果:RGD MMC、MMC组抑瘤率分别为77.6%和67.4%;与对照组比较差异均有统计学意义(P<0.05);RGD MMC组、MMC组肿瘤生长速度明显慢于对照组和RGD组;RGD MMC组、MMC组肿瘤体积分别为(351.4±86.5)mm3及(520.6±121.9)mm3,均明显小于对照组(1613.9±460.2)mm3(P<0.05);RGD MMC组、MMC组肿瘤重量分别为(366.5±93.4)mg及(534.7±135.6)mg,均明显小于对照组(1639.5±479.2)mg(P<0.05)。结论:FN拮抗剂RGD肽可协同MMC抑制荷膀胱癌T24裸鼠肿瘤的生长;RGD肽联合MMC治疗膀胱移行细胞癌可能有较好的临床应用前景。     

表阿霉素纳米胶束靶向治疗大鼠移植性肝癌

目的 探讨键合表阿霉素纳米胶束(EPI-NPs)在大鼠移植性肝癌模型肝内的分布及药效.方法 制备具有靶向控释作用的EPI-NPs,Walker-256细胞直接注射法制作大鼠移植性肝癌模型,通过肝动脉灌注给药(EPI含量均为2 mg/kg),利用组织荧光和匀浆荧光技术对比分析EPI-NPs和表阿霉素(EPI)在肝内的分布特点,并作药效对比.结果 EPI-NPs组肿瘤组织的EPI荧光强度高于肝组织(P＜0.05),而EPI组则表现为平均分布;EPI-NPs组在肿瘤及肝内的EPI荧光强度均高于EPI组(P＜0.05).EPI-NPs组大鼠肝移植瘤的体积抑瘤率及质量抑瘤率分别为72.96％和68.19％,EPI组的体积抑瘤率及质量抑瘤率分别为39.16％和35.33％,两者差异均有统计学意义(P＜0.05).EPI-NPs组生存率高于EPI组(P＜0.05).结论 EPI-NPs具有良好的肿瘤组织靶向性和抑瘤效果.     

quercetin抑制肝癌增长过程中Fas基因表达变化

目的 探讨三磷酸肌醇(IP3)和Fas基因表达变化在quercetin治疗裸鼠移植人肝癌中的作用.方法 以裸鼠移植人肝癌为研究对象,对照组腹腔注入含0.04%DMSO的RPMI1640培养基0.05 ml/g,Quercetin治疗组腹腔注入quercetin 1 mg·kg-1·d-1,3周后观察肝癌增长情况,并应用同位素试剂盒检测肝癌组织IP3含量,RT-PCR分析癌组织Fas mRNA表达,Western blotting分析肝癌组织Fas蛋白表达.结果 治疗组肝癌体积和重量均显著低于对照组[体积(15.8±10.1)mm3 vs (52.3±26.5)mm3,t=3.853,P=0.003);重量(44.8±10.4)mg vs(91.3±31.4)mg,t=3.391,P=0.004],IP3含量显著低于对照组[(13.4±1.4)pmol/mg protein vs(35.3±6.6)pmol/mg protein,t=8.322,P=0.000],Fas mRNA表达显著高于对照组[RI(灰度与面积之积的相对强度)0.52±0.13 vs 0.36±0.09,t=2.433,P=0.038],Fas蛋白表达显著高于对照组[RI(灰度与面积之积的相对强度)1.72±0.27 vs 1.08±0.15,t=5.056,P=0.000].结论 Quercetin能减少IP3生成,上调肝癌组织Fas基因表达,抑制裸鼠移植人肝癌增长.     

人结直肠癌化疗药物的裸鼠体内敏感性实验

目的探讨活体内人结直肠癌对5种化疗药物的敏感性。方法用9例结直肠癌患者的肿瘤组织建立结直肠癌裸鼠皮下移植瘤模型,分别应用5-氟尿嘧啶(5-FU)、奥沙利铂(LOHP)、丝裂霉素(MMC)、阿霉素(ADM)及伊立替康(CPT-11)对移植瘤进行干预治疗,观察该5种药物对裸鼠皮下移植瘤生长的影响。结果对照组裸鼠皮下移植瘤的体积明显大于其余5个化疗药物组;6组裸鼠肝肺均无转移。5种化疗药物对9例患者的裸鼠皮下移植瘤的最低和最高抑瘤率5-FU为23.6%和54.9%;LOHP为23.7%和69.5%;CPT-11为23.6%和82.6%;MMC为24.1%和48.1%;ADM为5.8%和20.7%。LOHP、CPT-11、5-FU和MMC组分别有7例、6例、4例和1例患者的裸鼠皮下移植瘤抑瘤率在40.0%以上。9例患者的移植瘤中,3种药物抑瘤率均在40.0%以上者3例,2种药物抑瘤率均在40.0%以上者4例,1例除CPT-11的抑瘤率为82.6%外,其余4种药物的抑瘤率均在30.0%以下,1例5种化疗药物的抑瘤率均在31.0%以下。5个化疗药物组抑瘤率之间的差异具有统计学意义(H=24.061 2,P=0.000 1),其中,与ADM组相比,5-FU组、MMC组、LOHP组及CPT-11组的抑瘤率较高(P<0.05),后4组之间抑瘤率的差异均无统计学意义(P>0.05)。结论同一结直肠癌患者的裸鼠皮下移植瘤对不同化疗药物的敏感性存在较大差异,同一种化疗药物对不同结直肠癌患者的裸鼠皮下移植瘤的抑瘤率也存在较大差异。在5种化疗药物中,LOHP和CPT-11对裸鼠皮下结直肠癌移植瘤的抑瘤率最高,其次为5-FU和MMC。     

5-氟尿嘧啶硅橡胶囊控释植入剂治疗Wistar大鼠肝癌的实验研究

在Ｗｉｓｔａｒ大鼠肝左叶被膜下接种Ｗａｌｋｅｒ－２５６系肝癌组织６天后，将５－氟尿嘧啶硅橡胶囊控释植入剂（５－ＦｕＣＩ）植入肿瘤所在的肝左叶，观察其抑瘤率及带瘤大鼠生存时间，并与对照组及５－ＦｕＣＩ放置于肝右叶组相比较。结果表明：３组动物３０天生存率分别为１００％、３３．３％及５０％。实验组动物抑瘤率为９６．３％，且动物生存时间较其它两组明显延长（Ｐ＜０．０５），光镜下可见大量癌细胞坏死。     

姜黄素联合舒尼替尼治疗人786-0肾癌裸鼠移植瘤

目的:探讨姜黄素联合舒尼替尼对抑制人肾癌细胞系786-0裸鼠移植瘤生长有无增效作用.方法:将32只人肾细胞癌裸鼠随机分为4组,阴性对照组以0.9%生理盐水0.2 mL腹腔注射,舒尼替尼组以舒尼替尼40 mg/kg腹腔注射,姜黄素组以姜黄素100 mg/kg腹腔注射,研究组以舒尼替尼联合姜黄素腹腔注射.结果:研究组较其他3组具有更强的抑瘤作用,远期效果高于舒尼替尼组(P<0.05);研究组比舒尼替尼组抗血管增殖作用更加明显(P<0.01);凋亡指数明显高于其他3组(P<0.05).结论:姜黄素联合舒尼替尼抑瘤作用明显强于单独应用舒尼替尼或姜黄素.     

白藜芦醇与氟尿嘧啶对小鼠肝癌的联合治疗作用

目的　探讨白藜芦醇单独及其与氟尿嘧啶 (5 Fu)联合应用对小鼠移植性肝癌的抑制作用。方法　利用小鼠移植性肝癌H2 2 模型研究白藜芦醇的体内抑瘤作用以及其对氟尿嘧啶抑瘤作用的影响。结果　白藜芦醇治疗组能不同程度抑制小鼠肝脏移植瘤的生长 ,10 0mg/kg和 15mg/kg的白藜芦醇治疗时抑瘤率分别为 36 6 %和 4 9 3% ,与对照组比较有明显差异 (P <0 0 1) ;同时发现白藜芦醇与氟尿嘧啶合用能增加氟尿嘧啶的抑瘤率 ,单用 2 0mg/kg或 10mg/kg的氟尿嘧啶 ,抑瘤率分别为 5 3 1% ,4 3 8% ,而合用 10mg/kg的白藜芦醇后抑瘤率分别为 77 3%、72 7% ,两者有显著性差异 ,且无明显的毒性反应。结论　白藜芦醇能增强氟尿嘧啶的抗癌作用 ,降低其毒性 ;白藜芦醇作为生化调节剂可能用于肿瘤联合化疗。     

联合TNP-470和MMC对小鼠肝癌术后复发和转移防治的实验研究

目的　研究血管形成抑制剂 TNP- 4 70联合 MMC对小鼠原位种植性肝癌术后复发和转移的防治作用。方法　原位肝癌模型小鼠切除肿瘤后建成肝癌切除术后小鼠模型 6 0只 ,随机分为四组 ,1对照组 :隔日皮下注射 3%酒精溶剂 ;2MMC组 :每周一次腹腔注射 MMC(2 m g/ Kg) ;3TNP- 4 70组 :隔日皮下注射 TNP- 4 70 (30 mg/ kg) ;4 TNP- 4 70 +MMC组 ;隔日皮下注射 TNP- 4 70 (30 m g/ kg) ,每周一次腹腔注射 MMC(2 mg/ kg) ,用药至小鼠死亡。检测小鼠存活时间、各组复发率、复发瘤体积、处理前后腹围。　结果　 1TNP- 4 70组及联合用药组较 MMC组和对照组生厚时间明显延长 (P<0 .0 5 ) ;2联合用药组较 MMC组复发率明显减少 ,复发瘤体积亦减少 (P<0 .0 5 ) ;3联合用药组较单药组小鼠腹围明显减少 (P<0 .0 5 )。结论　联合 TNP- 4 70及 MMC能明显提高单药对小鼠肝癌切除术后复发和转移的效果。     

MDR1特异性核酶逆转肝癌多药耐药的实验研究

目的探讨MDR1核酶（N2A＋tRNAi^met-iMDRl-sRz，sRz）在裸鼠体内逆转人肝癌组织多药耐药（MDR）的可行性。方法将原发性MDR人肝癌组织裸鼠原位移植模型第2代随机分为A组（空白对照组：生理盐水40μl＋Lipofect AMINE^TM2000 10μ1）、B组（阴性对照组：N2A＋tRNAi^met 10μg／40μl＋Lipofect AMINE^TM2000 10μl）和C组（核酶组：sRz 10μg／40μl＋LipofectAMINE^TM2000 10μl），均开腹瘤内注射。瘤内注药1周后用表阿霉素15mg／kg腹腔注射，每周1次，连续4周。彩色B超测量肿瘤体积。化疗结束后1周处死裸鼠，RT-PCR、Western blot法检测肿瘤中MDR1 mRNA及其蛋白P-gp的表达。结果C组每次化疗后肿瘤体积均较前缩小（F=659．99，P〈0．05）。除第1次化疗外，其余各次化疗后C组的抑制率均高于A、B组（F=35．36，12．77，97．60，P〈0．05）。化疗结束后，C组与瘤源以及A、B组相比，肿瘤组织中MDR1 mRNA和P-gp的表达明显降低（F=45．36，3590．40，P〈0．05）。结论sRz可有效降低肝癌细胞表达MDR1 mRNA和P-gp，一定程度上逆转MDR，提高E-ADM的化疗效果。单纯E-ADM化疗可使肝癌组织MDR1 mRNA和P-gp表达升高，诱导MDR的产生。     

卡培他滨抑制裸鼠肝癌切除术后复发转移的作用

目的探讨血小板衍化内皮细胞生长因子（PD-ECGF）依赖的化疗药卡培他滨（Capecitabine,CAP）对肝癌切除术后复发转移的作用。方法用免疫组化方法检测18例LCI-D20裸鼠人肝癌高转移模型中肝癌和肺转移灶中的PD-ECGF表达。用24只LCI-D20裸鼠,于肝癌组织原位种植后第10天行根治性肝癌切除术,术后第3天分别采用CAP和5-氟尿嘧啶治疗。停药后第3天处死裸鼠,观察肝内有无肿瘤复发。若有则测量复发灶的长短径。检测裸鼠肝功能和血浆甲胎蛋白（AFP）水平,并用HE染色检测肺转移。结果18例肝癌和肺转移灶组织中均表达PD-ECGF。CAP治疗后,肝内复发癌灶体积［（168±206）mm     

干扰素-α抑制高转移潜能人肝癌裸鼠肝细胞生长因子及血管内皮生长因子的表达

目的 观察干扰素-α(IFN-α)对高转移潜能人肝癌裸鼠模型中血管内皮生长因子(VEGF)、肝细胞生长因子(HGF)mRNA表达的影响.方法 应用绿色荧光蛋白转染的人高转移肝癌细胞株HCC-LM3建立高转移潜能人肝癌裸鼠模型LCI-D20,种植后第2天开始分别使用IFN-α 1.5×104 U/(kg·d)(治疗组,n=12)或生理盐水(对照组,n=12)皮下注射,28 d后处死裸鼠,比较肝脏肿瘤的大小和肝内转移,免疫组织化学检测肿瘤微血管密度(MVD),实时荧光定量聚合酶链反应(PCR)检测肿瘤HGF和VEGF表达的变化.结果治疗组、对照组的肝内肿瘤大小分别为(0.11±0.03)cm3、(0.99±0.37)cm3(P<0.05);肝内转移率分别为33.3%(4/12)、83.3%(10/12)(P<0.05);肝内转移数目分别为0.67±0.31个比1.91±0.43个(P<0.05);肿瘤内MVD分别为3.19±0.52、4.85±0.72(P<0.05);肿瘤VEGF mRNA表达(-△CT)分别为-8.16±0.54、-6.95±0.86(P<0.05);HGF mRNA表达分别为-11.62±0.63、-10.56±0.48(P<0.05).结论 IFN-α对HGF及VEGF表达的抑制可能是其抗肿瘤血管生成作用、抑制肿瘤生长转移作用的机制之一.     

Effects of prostacyclin on hepatic metastases from human pancreatic cancer in the nude mouse

Human pancreatic cancer is an aggressive malignancy, with systemic metastases ultimately accounting for its grave prognosis. Arachidonic acid metabolites known to affect platelet function also interfere with tumor growth and metastases. We evaluated the effect of prostacyclin on the hepatic metastases of a human pancreatic cancer in a nude mouse model. The mean surface area of tumor on the liver was significantly reduced in all treatment groups. In the control group 485 mm2 of tumor was present on the liver surface. Animals treated with 200 micrograms of prostacyclin 0.5 hr prior to the injection of tumor cells had 21 mm2 of tumor present on the liver surface (P = 0.004). Similarly, 400 micrograms of prostacyclin caused a reduction of tumor surface area to 20 mm2 (P = 0.004). The maximal reduction of tumor surface area, 11 mm2, was observed when 200 micrograms of prostacyclin was given 0.5 hr prior to and 4.0 hr after the injection of tumor cells (P = 0.003). For the group given 200 micrograms of prostacyclin 4.0 hr after the injection of tumor, the surface area of tumor was 85 mm2 (P = 0.017). The number of tumor colonies on the liver surface was significantly reduced from 20 to 11 when 200 micrograms of prostacyclin was administered intraperitoneally 0.5 hr before and 4.0 hr after the injection of tumor cells (P = 0.047). These results indicate that prostacyclin has antimetastatic activity on hepatic metastases from a human pancreatic adenocarcinoma in the nude mouse.     

Regional hepatic chemotherapy using an implantable drug infusion pump

Regional infusion of chemotherapeutic agents in the treatment of liver cancer can greatly increase tumor exposure to certain drugs. Exposure is 100 times greater with floxuridine, 6 times greater with mitomycin C, and 6 times greater with BCNU. The Model 400 Infusaid implantable, refillable drug infusion pump overcomes much of the discomfort and inconvenience associated with previously employed extracorporeal systems. Our experience with our first 50 patients has been presented herein. Forty-one patients had metastatic colorectal cancer, 3 primary cancers, and 6 other metastatic cancers. Eleven pumps and 11 catheters were implanted at laparotomy. Thirty-nine patients had their pumps integrated to angiographically placed catheters. In over 260 patient months there were no pump malfunctions and only one infection. There were no vascular complications in the patients with angiographically placed catheters. Chemotherapeutic programs included floxuridine, floxuridine and radiotherapy, or floxuridine with mitomycin C and BCNU. In 18 patients with evaluable metastatic colorectal cancer who received hepatic arterial combination chemotherapy, there were therapeutic responses in 13 and disease stabilization in 4. The pumps were well tolerated by patients. They offer a reasonable approach to long-term ambulatory regional hepatic chemotherapy.     

不同化疗药对人肝癌细胞BEL-7404端粒酶活性的影响

目的观察几种常用化疗药物对人肝癌BEL-7404细胞端粒酶活性的影响。方法利用端粒重复扩增实验(TRAP)结合非常性聚丙烯酰胺凝胶电泳银染法,测定BEL-7404细胞经过多种化疗药物(顺铂、阿霉素、丝裂霉素、长春新碱)不同浓度和时间作用后端粒酶活性的变化。结果当各种药物大剂量处理细胞24 h后再去除药物,顺铂对端粒酶的活性完全抑制,丝裂霉素有部分抑制,阿霉素和长春新碱无抑制作用;小剂量药物处理细胞3d,其结果同大剂量相似。结论高浓度顺铂和丝裂霉素C在短时间内或低浓度长时间作用对人肝癌BEL-7404细胞端粒酶活性有显著抑制作用,抑制作用可能与药物的作用浓度和时间有关。     

Intravesical bacillus Calmette-Guérin is superior to mitomycin C in reducing tumour recurrence in high-risk superficial bladder cancer: a meta-analysis of randomized trials

OBJECTIVE: To assess, in a systematic review and meta-analysis, the relative effectiveness of intravesical mitomycin C and bacillus Calmette-Guérin (BCG) for tumour recurrence, disease progression and overall survival in patients with medium- to high-risk Ta and T1 bladder cancer. METHODS: The major medical databases were searched comprehensively up to June 2003, and relevant journals hand-searched for randomized controlled trials, in any language, that compared intravesical mitomycin C with BCG in medium- to high-risk patients with Ta or T1 bladder cancer. RESULTS: Twenty-five articles were identified but only seven were considered eligible for the analysis. This represented 1901 evaluable patients in all, 820 randomized to mitomycin C and 1081 to BCG. Six trials had sufficient data for meta-analysis and included 1527 patients, 693 in the mitomycin and 834 in the BCG arm. There was no significant difference between mitomycin C and BCG for tumour recurrence in the six trials, with a weighted mean log hazard ratio, LHR, (variance) of -0.022 (0.005). However, there was significant heterogeneity between trials (P = 0.001). A subgroup analysis of three trials that included only high-risk Ta and T1 patients indicated no heterogeneity (P = 0.25) and a LHR for recurrence of -0.371 (0.012). With mitomycin C used as the control in the meta-analysis, a negative ratio is in favour of BCG and, in this case, was highly significant (P < 0.001). The seventh trial (in abstract form only) used BCG in low doses for two arms of the trial (27 mg and 13.5 mg) compared with a standard dose of mitomycin C (30 mg), and reported a significantly lower recurrence rate with BCG (27 mg) than for mitomycin C (P = 0.001). Only two trials included sufficient data to analyse disease progression and survival, representing 681 patients (338 randomized to BCG and 343 to mitomycin C). There was no significant difference between mitomycin C and BCG for disease progression, with a LHR of 0.044 (0.04) (P = 0.16), or survival, at -0.112 (0.03) (P = 0.50). Adverse events were slightly more frequent with BCG. Local toxicity (dysuria, cystitis, frequency and haematuria) were associated with both mitomycin C (30%) and BCG (44%). Systemic toxicity, e.g. chills, fever and malaise, occurred with both agents (12% and 19%, respectively) although skin rash was more common with mitomycin C. CONCLUSION: Tumour recurrence was significantly lower with intravesical BCG than with mitomycin C only in those patients at high risk of tumour recurrence. However, there was no difference in disease progression or survival, and the decision to use either agent might be based on adverse events and cost.     

树突状细胞联合细胞因子诱导的杀伤细胞对原发性小肠恶性黑色素瘤生长及肝转移的抑制作用

目的 探讨树突状细胞(DC)与同源细胞因子诱导的杀伤细胞(CIK)共培养后对小肠恶性黑色素瘤生长和肝转移的抑制作用.方法 提取健康献血者、小肠恶性黑色素瘤患者外周血单核细胞,常规诱导出DC细胞与CIK细胞后,按照1∶5比例共培养14 d获得DC-CIK细胞.取原发性小肠恶性黑色素瘤手术切除的肝转移灶新鲜瘤组织块植入裸鼠小肠黏膜层,建立小肠恶性黑色素瘤肝转移模型.将56只裸鼠原位移植人小肠恶性黑色素瘤72 h后,分成7组,每组8只:(1)对照组;(2)丝裂霉素组;(3)健康人CIK细胞组;(4)健康人DC-CIK细胞组;(5)小肠恶性黑色素瘤自体CIK细胞组;(6)小肠恶性黑色素瘤自体DC-CIK细胞组;(7)小肠恶性黑色素瘤自体DC-CIK细胞+丝裂霉素组.对照组裸鼠注射生理盐水,其余各组裸鼠尾静脉注射相应的效应细胞,每只0.3 ml,细胞数为6×107个,丝裂霉素注射剂量为400 μg,每天1次,连续28 d.停药后72 h处死动物,切取肿瘤称质量,并检查肿瘤生长及肝转移情况.多组比较采用单因素方差分析,两两比较采用LSD法,率的比较采用x2检验.结果 成功建立小肠恶性黑色素瘤肝转移模型(HSIM-0603).对照组、丝裂霉素组、健康人CIK细胞组和DC-CIK细胞组、小肠恶性黑色素瘤患者自体CIK细胞组和DC-CIK细胞组及DC-CIK细胞+丝裂霉素组的肿瘤质量分别为(1.18±0.17)、(0.71±0.06)、(0.68±0.15)、(0.43±0.08)、(0.67±0.07)、(0.37±0.08)、(0.20±0.05)g;抑瘤率分别为0、39.82%、42.37%、63.56%、43.22%、68.64%、83.05%;肝转移分别为8、8、5、4、4、3、2只,各组比较,差异有统计学意义(F=152.300,x2=200.538,94.325,P＜0.05).结论 小肠恶性黑色素瘤肝转移模型可用于小肠恶性黑色素瘤的发病机制、侵袭、转移及治疗的研究,DC-CIK细胞治疗能抑制小肠恶性黑色素瘤的生长和肝转移.     

阿司匹林抑制核因子-κB增强索拉非尼对肝癌的促凋亡作用

目的 观察合用阿司匹林(Aspirin)与索拉非尼(Sorafenib)对肝癌生长转移的抑制作用和促凋亡作用并探讨其机制.方法 采用人肝癌裸鼠原位模型LCI-D20,分为对照组、Sorafenib 单用组(30 mg/kg灌胃,1d1次)、Sorafenib+ Aspirin合用组、Aspirin单用组(30 mg/kg灌胃,1 d 1 次),治疗4周后观察荷瘤小鼠生存期、肿瘤体积、肺转移,定量比较肿瘤细胞凋亡指数,观察各组荷瘤鼠生存期,检测各组核因子-κB (NF-κB)及IκBα表达.结果 对照组、Sorafenib治疗组、Sorafenib + Aspirin合用组、Aspirin治疗组肿瘤体积分别为(4.76±0.51)、(1.41±0.08)、(0.66 ±0.12)和(4.58±0.47) cm3;肺转移灶数目分别为(189±21)、(96±15)、(30±17)和(92±18)个;中位生存期分别为72、98、112、80 d.肿瘤凋亡指数分别为(2.6±1.1)％、(8.6±3.7)％、(24.3±6.9)％和(6.8±1.5)％;与Sorafenib治疗组比较,Sorafenib+ Aspirin合用明显降低肿瘤体积(P＜0.05)、抑制肺转移灶数目(P＜0.01),延长荷瘤鼠生存期(P＜0.05)和促进肿瘤细胞凋亡(P＜0.05).Sorafenib 在肝癌中具有下调IκBα和上调NF-κB-p65的作用而合用Aspirin可逆转此作用.结论 Aspirin通过抑制NF-κB活化,进一步增强Sorafenib对肝癌凋亡的促进作用及对肝癌生长转移的抑制作用,并延长荷瘤鼠生存期.     

Effectiveness of a single immediate mitomycin C instillation in patients with low risk superficial bladder cancer: short and long-term followup

PURPOSE: We analyze the impact of a single mitomycin C instillation in patients with low risk superficial bladder cancer with short and long-term followup. MATERIALS AND METHODS: A total of 131 patients with low risk superficial bladder cancer were included in a prospective randomized controlled trial. All patients had a 3 cm or less single, papillary, primary or recurrent tumor and were disease-free for more than 1 year. Patients with muscular invasion, G3 tumor or bladder carcinoma in situ on pathological examination were excluded from study. The tumor was completely resected before patients were randomized into 2 arms of no further treatment (control group) and a single immediate instillation of 30 mg mitomycin C (mitomycin C group). Recurrences were considered early within the first 2 years of followup. RESULTS: At 24-month followup the recurrence-free interval was significantly increased, and recurrence, and recurrence and tumor per year rates were decreased in the mitomycin C compared to the control group. However, at long-term followup these differences were not statistically significant and the recurrence-free interval curves were parallel. A shorter hospital stay and catheterization period were noted in the mitomycin C group compared to the control group, which were not significant. Early recurrences were concentrated in the first year in the control but not in the mitomycin C group. A significant relationship between early and late recurrences was found in the mitomycin C but not in the control group. CONCLUSIONS: Our analysis confirms the positive effect of a single immediate mitomycin C instillation in patients with low risk superficial bladder cancer. This benefit is limited to early recurrence and is not maintained with long-term followup. Thus, this approach is an alternative to observation or endovesical chemotherapy. Our study also suggests that cell implantation as a mechanism of early recurrence can be controlled with a single mitomycin C instillation.     

术中腹腔内温热灌注化疗在胃癌治疗中的应用

目的探讨术中腹腔内温热灌注化疗对胃癌术后腹腔种植转移和生存期的影响。方法将212例进展期胃癌根治性切除术后患者随机分成观察组92例,术中予以腹腔温热灌洗化疗(丝裂霉素30mg、顺铂100mg溶于蒸馏水2000ml中,加温至43℃～45℃,灌入腹腔保留30min后吸尽)和术后氟尿嘧啶(5-FU)10～15mg/kg、丝裂霉素(MMC)0.1～0.15mg/kg、阿霉素(ADM)0.5～1mg/kg静脉化疗,每周1次,2～3次为1疗程;对照组120例,术中用蒸馏水2000ml常规冲洗,术后按上述方法单纯静脉化疗。对两组患者术后腹腔种植转移率及1、3、5年生存率进行比较。结果观察组与对照组术后2年内腹腔种植转移率分别为14.1%和37.5%(P<0.01)。观察组术后1、3和5年生存率分别为98.9%、68.5%和52.2%;对照组为95.0%、56.7%和37.5%,两组3年和5年生存率差异有统计学意义(P<0.05)。结论术中温热灌注化疗具有杀灭腹腔游离癌细胞的作用,对进展期胃癌根治术后腹腔种植转移复发有较好的防治作用,能明显提高患者术后生存率。