重组人血管内皮抑制素注射液联合化疗治疗老年晚期非小细胞肺癌的效果观察

目的探讨重组人血管内皮抑制素注射液联合化疗治疗老年晚期非小细胞肺癌的临床效果。方法选择患者80例,分为两组,每组各40例,对照组化疗方案：多西他塞75mg／m2联合吉西他滨1000mg／m2,观察组在对照组的基础上使用重组人血管内皮抑制素注射液,比较两组患者治疗前后的生活质量KPS评分,并统计两组的近期疗效。结果治疗后观察组的生活质量KPS评分显著高于对照组（P〈0．05）,观察组的有效率为35．0％,显著高于对照组的10．0％（P〈0．05）。结论重组人血管内皮抑制素注射液联合化疗应用于晚期非小细胞肺癌患者,能显著提高患者的生活质量,延长生存时间,值得临床推广。     

罗格列酮增强顺铂对肺腺癌裸鼠移植瘤生长的抑制作用

目的观察罗格列酮(ROZ)和顺铂(DDP)合用对人肺腺癌A549细胞裸小鼠移植瘤生长的抑制作用,并初步探讨其作用机制。方法采用A549细胞株建立人肺腺癌裸鼠模型,将28只成瘤雌裸小鼠随机分成7组:①对照组(生理盐水0.2ml);②DDP低剂量组(1mg.kg-1);③DDP高剂量组(4mg.kg-1);④ROZ低剂量组(10mg.kg-1);⑤ROZ高剂量组(30mg.kg-1);⑥DDP低剂量组+ROZ低剂量组;⑦DDP低剂量组+ROZ高剂量组,隔天腹腔注射给药,共8次。于最后一次给药后48h处死各组小鼠,收集瘤标本行光镜观察,免疫组化检测PPARγ、PTEN和pAkt蛋白表达情况。结果①各实验组肿瘤的生长明显受到抑制,瘤质量明显低于对照组(P<0.01)。低、高剂量ROZ联合用药组较低剂量顺铂组抑瘤作用明显增强(P<0.05),其瘤重抑制率分别为52.11%和83.8%。②免疫组化:低、高剂量罗格列酮组与对照组比较,PPARγ、PTEN的表达上调,而pAkt的表达呈现下调,差异具有显著性(P<0.05),联合用药组该调节作用进一步增强(P=0.00)。③不良反应:高剂量顺铂组出现不良反应,其余各组无明显不良反应。结论罗格列酮能够增强顺铂对人肺腺癌A549细胞裸鼠移植瘤生长的抑制作用,其作用机制可能与罗格列酮激活PPARγ,上调PTEN的表达和抑制pAkt的表达有关。     

In vitro and in vivo anti-tumor activities of a gemcitabine derivative carried by nanoparticles

Gemcitabine (Gemzar(?)) is the first line treatment for pancreatic cancer and often used in combination therapy for non-small cell lung, ovarian, and metastatic breast cancers. Although extremely toxic to a variety of tumor cells in culture, the clinical outcome of gemcitabine treatment still needs improvement. In the present study, a new gemcitabine nanoparticle formulation was developed by incorporating a previously reported stearic acid amide derivative of gemcitabine into nanoparticles prepared from lecithin/glyceryl monostearate-in-water emulsions. The stearoyl gemcitabine nanoparticles were cytotoxic to tumor cells in culture, although it took a longer time for the gemcitabine in the nanoparticles to kill tumor cells than for free gemcitabine. In mice with pre-established model mouse or human tumors, the stearoyl gemcitabine nanoparticles were significantly more effective than free gemcitabine in controlling the tumor growth. PEGylation of the gemcitabine nanoparticles with polyethylene glycol (2000) prolonged the circulation of the nanoparticles in blood and increased the accumulation of the nanoparticles in tumor tissues (>6-fold), but the PEGylated and un-PEGylated gemcitabine nanoparticles showed similar anti-tumor activity in mice. Nevertheless, the nanoparticle formulation was critical for the stearoyl gemcitabine to show a strong anti-tumor activity. It is concluded that for the gemcitabine derivate-containing nanoparticles, cytotoxicity data in culture may not be used to predict their in vivo anti-tumor activity, and this novel gemcitabine nanoparticle formulation has the potential to improve the clinical outcome of gemcitabine treatment.     

重组人内抑素的抗肿瘤活性

目的观察重组人内抑素抗肿瘤活性及对血管内皮细胞增殖的抑制作用。方法用人癌裸鼠移植性肿瘤及小鼠移植性肿瘤模型对重组人内抑素进行抗肿瘤药效学观察,用MTT法观察其对血管内皮细胞及肿瘤细胞增殖的抑制作用。结果重组人内抑素,可明显抑制人胃癌BGC803和人乳腺癌B37裸鼠移植性肿瘤的生长,对小鼠肝癌H22实体瘤亦呈一定的抑制作用。MTT试验结果显示重组人内抑素可抑制人胎脐静脉血管内皮细胞ECV304的增殖,对人结肠癌HCT-8等肿瘤细胞的增殖无影响。结论重组人内抑素具有较强的抗肿瘤作用,其作用机理可能与抑制血管内皮细胞增殖、抑制肿瘤新生血管形成有关。     

芦荟多糖增强顺铂对肺腺癌裸鼠移植瘤生长的抑制作用

目的 观察芦荟多糖（Aloe polysaccharide,AP）和顺铂（DDP）合用对人肺腺癌A549细胞裸小鼠移植瘤生长的抑制作用,并初步探讨其作用机制。方法 采用A549细胞株建立人肺腺癌裸鼠模型,将35只,♀,成瘤裸小鼠随机分为7组：对照组（生理盐水0.2 mL）;DDP低剂量组（1.0 mg·kg^-1）;DDP高剂量组（5 mg·kg^-1）;AP低剂量组（10 mg·kg^-1）;AP高剂量组（30 mg·kg^-1）;DDP低剂量组＋AP低剂量组;DDP低剂量组＋AP高剂量组,隔天腹腔注射给药,共8次。于最后1次给药后48 h处死各组小鼠,收集瘤标本行光镜观察,免疫组化检测p53和bcl-2蛋白表达情况。结果 各实验组肿瘤的生长明显受到抑制,瘤质量明显低于对照组（P〈0.01）。低、高剂量AP联合用药组较低剂量DDP组抑瘤作用明显增强（P〈0.05）,其瘤重抑制率分别为49.34%和82.61%。高剂量AP组与对照组比较,p53和bcl-2的表达均下调,差异具有统计学意义（P〈0.05）,联合用药组该调节作用进一步增强。高剂量DDP组出现不良反应,其余各组无明显不良反应。结论 AP能够增强DDP对人肺腺癌A549细胞裸鼠移植瘤生长的抑制作用,其作用机制可能与AP抑制p53和bcl-2的表达有关。     

The therapeutic efficacy of angiostatin against weakly- and highly-immunogenic 3LL tumors

BACKGROUND: Antiagiogenesis represents a promising approach to cancer therapy. We have previously demonstrated that the antitumor effects of endostatin, one of the most potent angiostatic agents, could be enhanced when combined with immunotherapy. Our current study evaluated whether anti-tumor immune response could also potentiate the therapuetic efficacy of another antiangiogenic drug, angiostatin. METHODS AND RESULTS: Using Matrigel assay, we showed that our preparation of recombinant angiostatin possessed potent anti-angiogenic activity in vivo. The antitumor effects of recombinant angiostatin were tested against weakly-immunogenic 3LL Lewis lung carcinoma versus its highly immunogenic variant 3LL-C75. We showed that angiostatin inhibited the growth of 3LL-C75 more potently than that of 3LL tumor, suggesting that the host's immune response potentiates the antitumor effects of angiostatin. This conclusion was further supported by the finding that the antitumor activity of angiostatin against 3LL-C75 tumor was lower in immunodeficient nude mice in comparison with immunocompetent mice. Immunization of C57BL/6 mice with 3LL-C75 cells stimulated the antitumor immunity and inhibited the growth of parental 3LL tumor. Angiostatin treatment of immunized mice further enhanced the antitumor effect of tumor vaccination. CONCLUSION: Antitumor immune response could complement the therapeutic efficacy of angiostatin.     

重组人血管内皮抑制素联合GP方案治疗晚期非小细胞肺癌37例临床观察

目的观察重组人血管内皮抑制素（恩度）联合GP方案治疗晚期非小细胞肺癌（NSCLC）的疗效和毒副反应。方法经病理学或细胞学检查证实的37例晚期NSCLC患者,包括鳞癌21例,腺癌16例。吉西他滨1000mg／m^2,静脉滴注,第1、8天;顺铂80mg／m^2,静脉滴注,分3d给予;恩度15mg／d,静脉滴注,第1～14天,21d为1个周期。每例患者至少完成2个周期。根据WHO疗效评定及毒副反应分级标准,观察其近期疗效、疾病进展时间及毒副反应。结果37例晚期NSCLC患者中,CR1例,PR15例,SD14例,PD7例,总有效率（CR＋PR）43．2％。中位疾病进展时间为5．2个月。毒副反应主要为血液学、消化道毒性,Ⅲ-Ⅳ度中性粒细胞减少占32．4％,Ⅲ-Ⅳ度血小板减少占20．5％,未见与化疗相关的死亡。结论恩度联合GP方案治疗晚期NSCLC近期客观疗效较高,安全性好。     

A randomized phase II study of recombinant human endostatin plus gemcitabine/cisplatin compared with gemcitabine/cisplatin alone as first-line therapy in advanced non-small-cell lung cancer

Purpose Studies indicate that recombinant human endostatin (rh-endostatin) can inhibit tumor endothelial cell proliferation, angiogenesis, and tumor growth. This study assessed the efficacy of the combination of standard gemcitabine plus cisplatin chemotherapy with rh-endostatin in patients with non-small-cell lung cancer (NSCLC). Patients and Methods Chemotherapy-naive patients with stage IIIB to IV NSCLC were randomly (1:1) assigned to receive gemcitabine/cisplatin chemotherapy alone or with 7.5 mg/ m² of intravenously rh-endostatin on days 1 to 14 of each 3-week cycle. The primary end point was objective response rate (ORR). Results Baseline characteristics were similar between treatment arms. The best ORRs for rh-endostatin arm (n = 33) and chemotherapy-alone arm were 37.5% (95% CI: 21.3 to 47.2%) and 28.6% (95% CI: 19.8 to 37.6%), respectively. Median survival was 12.4 months in the rh-endostatin arm and 9.8 months in the chemotherapy-alone arm, and 1-year survival was 51.6% and 38.7%, respectively. Mild palpitions, diarrhea, and liver dysfunction were the most common rh-endostatin-related adverse events. Grade 3/4 hematological toxicities were all reported similar for patients in the two arms. Conclusion The addition of rh-endostatin to gemcitabine plus cisplatin chemotherapy for first-line treatment of NSCLC improves objective response and may improve survival.     

重组人血管内皮抑制素联合GP方案治疗晚期非小细胞肺癌37例临床观察

目的 观察重组人血管内皮抑制素(恩度)联合GP方案治疗晚期非小细胞肺癌(NSCLC)的疗效和毒副反应.方法 经病理学或细胞学检查证实的37例晚期NSCLC患者,包括鳞癌21例,腺癌16例.吉西他滨1 000 mg/m2,静脉滴注,第1、8天;顺铂80 mg/m2,静脉滴注,分3 d给予;恩度15 mg/d,静脉滴注,第1～14天,21 d为1个周期.每例患者至少完成2个周期.根据WHO疗效评定及毒副反应分级标准,观察其近期疗效、疾病进展时间及毒副反应.结果 37例晚期NSCLC患者中,CR 1例,PR 15例,SD 14例,PD 7例,总有效率(CR+PR)43.2%.中位疾病进展时间为5.2个月.毒副反应主要为血液学、消化道毒性,Ⅲ～Ⅳ度中性粒细胞减少占32.4%,Ⅲ～Ⅳ度血小板减少占20.5%,未见与化疗相关的死亡.结论 恩度联合GP方案治疗晚期NSCLC近期客观疗效较高,安全性好.     

重组人血管内皮抑制素联合化疗治疗晚期非小细胞肺癌的临床观察

目的:观察重组人血管内皮抑制素联合吉西他滨和奈达铂序贯给药治疗晚期非小细胞肺癌(NSCLC)的疗效和安全性。方法:将48例NSCLC患者随机分为观察组与对照组。观察组采用序贯给药方案:重组人血管内皮抑制素7.5 mg/m2(d1^d14)+吉西他滨1 000 mg/m2(d4、d11)+奈达铂80 mg/m2(d4)。对照组单用化疗方案:吉西他滨1 000 mg/m2(d1、d8)+奈达铂80 mg/m2(d1)。21 d为1个周期,治疗2个周期后评价有效率(RR)、疾病控制率(DCR)、药品不良反应。对于稳定期和有效的患者继续给予化疗2d14)+吉西他滨1 000 mg/m2(d4、d11)+奈达铂80 mg/m2(d4)。对照组单用化疗方案:吉西他滨1 000 mg/m2(d1、d8)+奈达铂80 mg/m2(d1)。21 d为1个周期,治疗2个周期后评价有效率(RR)、疾病控制率(DCR)、药品不良反应。对于稳定期和有效的患者继续给予化疗2⁴个周期直至疾病进展,随访生存时间。结果:观察组RR为33.3%,显著高于对照组的8.3%,差异有统计学意义(P<0.05);观察组DCR为87.5%,高于对照组的70.8%,但差异无统计学意义(P>0.05);观察组与对照组的中位生存时间分别为14、11个月,两组生存曲线比较观察组优于对照组(P<0.05)。在不良反应方面两组差异无统计学意义(P>0.05)。结论:重组人血管内皮抑制素联合吉西他滨和奈达铂序贯给药方案可提高患者的临床疗效及生存期,安全性好。     

携带Kringle 5基因重组腺病毒的构建及其对荷肺癌小鼠生存期的作用

目的：构建携带人纤溶酶原Kringle 5（K5）基因重组腺病毒并观察其在小鼠肺癌细胞中的表达和对荷TC-1瘤小鼠的生存期的影响。方法：构建携带人纤溶酶原K5基因表达框的腺病毒载体Ad-EF1α-K5，用RT-PCR法检测腺病毒感染TC-1细胞后K5 mRNA的表达，用免疫沉淀和Western bloting法检测腺病毒感染TC-1细胞后K5蛋白的表达。建立荷TC-1小鼠肺癌C57BL／6小鼠模型，观察重组腺病毒对荷瘤小鼠生存期的影响。取肿瘤组织做免疫组织化学染色并计数微血管密度。结果：携带K5基因的人V型腺病毒能有效感染小鼠肺癌TC-1细胞，在转录和翻译水平进行表达，能有效延长荷瘤鼠的生存期并降低肿瘤微血管密度。结论：腺病毒可作为便捷的载体携带K5基因感染肿瘤细胞，分泌表达K5蛋白，延长荷瘤小鼠生存期，可能与其通过抑制肿瘤区血管生成、遏制肿瘤区血供有关。     

重组人血管内皮抑素联合化疗治疗乳腺癌的实验研究

目的 研究重组人血管内皮抑素联合化疗方案对人乳腺癌裸鼠移植瘤模型的治疗效应,并进一步探讨其抑制肿瘤血管生成的作用机制。方法 将乳腺癌荷瘤裸鼠40只随机分为4组,分别为化疗组、内皮抑素组、联合用药组及对照组。化疗组给予长春瑞滨和顺铂;内皮抑素组给予重组人血管内皮抑素;联合用药组给予长春瑞滨,顺铂,和重组人血管内皮抑素;对照组给予等量的生理盐水。给药期间测量肿瘤大小,实验结束取肿瘤称重,计算肿瘤体积,绘制肿瘤生长曲线并比较各组的抑瘤率。免疫组化方法检测各组肿瘤组织微血管密度（MVD）,VEGF,HIF-1α及P53的表达。结果 联合用药组抑瘤率为64.63％,化疗组抑瘤率为35.47％。联合用药组与其他3组MVD计数比较明显减少,差异有统计学意义（P〈0.05）。与对照组及化疗组相比,联合用药组的VEGF、HIF-1α和P53的表达均明显减少,其差异具有统计学意义（P〈0.05）。结论 重组人血管内皮抑素联合化疗能够有效控制裸鼠乳腺肿瘤生长,降低肿瘤MVD,其机制可能为下调VEGF及HIF-1α的表达。内皮抑素对P53的作用机制有待于更进一步的研究。     

重组Canstatin蛋白联合氟尿嘧啶治疗裸鼠结肠癌移植瘤的实验研究

目的探讨血管生成抑制剂Canstatin与细胞毒药物氟尿嘧啶（5-FU）联合应用治疗结肠癌的效果,以期探索结肠癌治疗新途径。方法结肠癌SW-480细胞（1×107/只）注射到30只裸鼠皮下,建立结肠癌皮下移植瘤模型。当肿瘤长至2--3 mm时,随机分6组。给药途径均为腹腔注射给药。治疗期间,定期用圆规和游标卡尺测量皮下移植瘤大小。疗程结束时,取下瘤体,常规病理切片,观察药物毒性反应,CD31免疫组化染色,检测肿瘤内微血管密度（MVD）。结果①各试验组肿瘤的生长明显受到抑制,瘤体质量明显低于对照组（P〈0.01）。5-FU＋Canstatin组低、高浓度联合治疗组抑瘤作用较对照组明显增强（P〈0.05）,其瘤重抑制率分别为74.76%和82.04%。②免疫组化：5-FU＋Canstatin组低浓度组（22.6±3.6）和5-FU＋Canstatin组高浓度组（15.0±2.8）治疗小鼠肿瘤组织内MVD显著低于对照组（36.4±5.6）和5-FU治疗组（31.2±4.0）（P〈0.05）,而5-FU治疗组与对照组间差异无统计学意义;③不良反应：各实验组未观察到明显毒性反应。结论重组人Canstatin蛋白能有效抑制人结肠癌生长,无明显毒副作用,为结肠癌治疗提供了新的有力的治疗方法。     

双环醇对顺铂联合吉西他滨致荷瘤小鼠肝肾损伤的保护作用

目的：建立顺铂（CDDP）联合吉西他滨（GEM）引起小鼠肝肾损伤动物模型,研究双环醇对CDDP/GEM联用致荷瘤小鼠肝肾损伤及骨髓毒性的保护作用。方法参考临床用药方案,建立CDDP/GEM联用致小鼠肝肾损伤模型。在模型建立的基础上,考察双环醇的保护作用：C57/BL小鼠接种Lewis肺癌后第6天开始腹腔注射CDDP（5mg·kg^-1×5）及GEM（50mg·kg^-1×2）,建立大剂量CDDP/GEM联用致小鼠肝肾损伤模型,同时灌胃给予双环醇（150、300mg·kg^-1）,以吉粒芬（100 g·kg^-1）作为阳性对照药。于开始给药后第6天处理动物,取瘤称重,全自动生化分析仪检测血清肝功能及肾功能生化指标,五分类血液分析仪进行血象分析。结果小鼠腹腔注射CDDP（5mg·kg^-1×5）及GEM （50mg·kg^-1×2）,在动物尚未出现大量死亡的情况下,能引起明显的肝肾损伤。双环醇150mg·kg^-1能显著降低上述方案CDDP/GEM引起的血清CR的升高,同时显著升高全血中NEUT和NEUT%。双环醇300mg·kg^-1亦有保护作用,但作用不显著。吉粒芬对CDDP/GEM联用引起的WBC、NEUT、NEUT%降低有显著升高作用。双环醇及吉粒芬与CDDP/GEM合用,对后者的抑瘤活性略有增加作用。结论双环醇在略增加CDDP/GEM抑瘤活性的基础上,150mg·kg^-1剂量对后者引起的荷瘤小鼠肝肾损伤及骨髓毒性具有良好的保护作用,300mg·kg^-1剂量组作用不及150mg·kg^-1剂量组,但均能降低荷瘤小鼠死亡率,值得临床关注。     

培美曲塞、顺铂联合重组人血管内皮抑制素治疗肺腺癌

目的观察培美曲塞、顺铂联合重组人血管内皮抑制素注射液（恩度）治疗肺腺癌的疗效与安全性。方法选择经病理及细胞学诊断明确的晚期肺腺癌初治患者52例,根据住院号随机分为观察组27例,对照组25例,观察组给予培美曲塞＋顺铂联合恩度治疗,对照组仅给予培美曲塞＋顺铂治疗,评价两组疗效及安全性。结果观察组客观有效率（48．1％）明显高于对照组（36．0％）（x2=7．82,P〈0．05）;观察组疾病控制率（92．6％）明显高于对照组（84．0％）（x2=4．05,P〈0．05）;观察组中位肿瘤进展时间（7．5个月）明显长于对照组（5个月）（t=5．71,P〈0．05）;两组在治疗期间均出现相似的不良反应,主要为白细胞减少、血红蛋白减少、血小板减少、恶心呕吐、便秘、心律失常、出血、乏力等,两组在不良反应分级情况差异均无统计学意义（均P〉0．05）。结论培美曲塞、顺铂联合恩度治疗肺腺癌疗效较单用化疗药疗效显著,且未增加不良反应,具有安全性,可作为肺腺癌的一线用药。     

艾瑞昔布联合5-氟尿嘧啶对裸鼠结肠癌移植瘤侵袭和转移的影响

目的 探讨艾瑞昔布联合5-氟尿嘧啶(5-Fu)对结肠癌HT-29细胞裸鼠移植瘤侵袭和转移的影响以及与环氧化酶-2(COX-2)、血管内皮生长因子-C(VEGF-C)、基质金属蛋白酶-9(MMP-9)的关系.方法 40只裸鼠构建人结肠癌HT-29细胞裸鼠皮下移植瘤模型,随机分为4组,每组10只,对照组(0.9％NaCl)...     

猕猴桃根抗肿瘤作用研究

目的评价猕猴桃根提取物的体外、内抗肿瘤活性。方法猕猴桃根活性成分的分离、纯化采用传统的天然产物化学方法,猕猴桃根先用甲醇回流提取,然后用乙酸乙酯、氯仿、正丁醇萃取。不同组分对体外培养的肿瘤细胞增殖的作用采用磺酰罗丹明B方法;猕猴桃根的体内抗肿瘤作用采用小鼠肿瘤和人肿瘤裸小鼠移植瘤模型评价。结果氯仿提取物对肿瘤细胞增殖抑制作用最强,甲醇提取物次之。体内实验证实氯仿提取物有效地抑制小鼠肝癌模型和人肝癌裸小鼠移植瘤模型的生长,抑制率大概在38.0%。结论猕猴桃根提取物有一定的抗肿瘤作用;其活性成分主要存在于极性较小的组分。     

Magnetic poly epsilon-caprolactone nanoparticles containing Fe3O4 and gemcitabine enhance anti-tumor effect in pancreatic cancer xenograft mouse model

We prepared magnetic (Fe(3)O(4)) poly epsilon-caprolactone (PCL) nanoparticles (mean diameter 164 +/- 3 nm) containing an anticancer drug (gemcitabine) using emulsion-diffusion method in order to develop more efficient drug delivery for cancer treatment. Nanoparticles were smooth, well individualized and homogeneous in size. The values of magnetizations for the magnetic PCL nanoparticles were observed around 10.2 emu/g at 2000 Oe magnetic field intensity and showed super-paramagnetic property. In case of the drug, the drug loading contents was 18.6% and entrapment efficiency was 52.2%. The anti-tumor effects caused by these particles were examined using nude mice bearing subcutaneous human pancreatic adenocarcinoma cells (HPAC) in vivo. We divided that these mice were randomly assigned to one of five treatment groups for experimental contrast. The antitumor effect was showed with 15-fold higher dose when compared to free gemcitabine. From the result, the magnetic PCL nanoparticles may provide a therapeutic benefit by delivering drugs efficiently to magnetically targeted tumor tissues, thus achieving safe and successful anti-tumor effects with low toxicity.     

血管生成抑制剂联合分化诱导剂治疗结肠癌的实验研究

目的通过建立人LOVO细胞结肠癌裸鼠皮下移植瘤模型,研究血管生成抑制剂（TNP-470）联合分化诱导剂（RA）抗结肠癌生长的效应,二者是否具有协同效果。方法建立人LOVO细胞结肠癌裸鼠皮下移植瘤模型,模型建立后分组治疗,按治疗方式分为对照组、TNP-470组、RA组和联合组（TNP-470＋RA）至治疗结束时处死裸鼠,测量皮下移植瘤重量,计算抑瘤率;检测肿瘤组织结肠癌细胞凋亡指数（AI）。结果裸鼠皮下移植瘤瘤重、抑瘤率,联合组和对照组及TNP-470组、RA组比较差异均有统计学意义（P〈0.05）,且TNP-470组、RA组和对照组之间差异亦有统计学意义（P〈0.05）。治疗组与对照组癌细胞AI比较,差异有统计学意义（P〈0.05）;且联合组与RA组和TNP-470组癌细胞的AI比较,差异也有统计学意义（P〈0.05）。结论血管生成抑制剂TNP-470与分化诱导剂RA联合治疗结肠癌裸鼠皮下移植瘤比TNP-470或RA单药治疗具有更强的抑瘤作用,TNP-470通过抑制肿瘤血管生成,切断肿瘤细胞的血供和营养供给,抑制结肠癌裸鼠皮下移植瘤的生长;而RA通过诱导肿瘤细胞凋亡,降低VEGF的表达抑制肿瘤的生长,二者联和应用,抗肿瘤效应明显增强。     

Magnetic poly ε-caprolactone nanoparticles containing Fe3O4 and gemcitabine enhance anti-tumor effect in pancreatic cancer xenograft mouse model

We prepared magnetic (Fe₃O₄) poly ε-caprolactone (PCL) nanoparticles (mean diameter 164 ± 3 nm) containing an anticancer drug (gemcitabine) using emulsion-diffusion method in order to develop more efficient drug delivery for cancer treatment. Nanoparticles were smooth, well individualized and homogeneous in size. The values of magnetizations for the magnetic PCL nanoparticles were observed around 10.2 emu/g at 2000 Oe magnetic field intensity and showed super-paramagnetic property. In case of the drug, the drug loading contents was 18.6% and entrapment efficiency was 52.2%. The anti-tumor effects caused by these particles were examined using nude mice bearing subcutaneous human pancreatic adenocarcinoma cells (HPAC) in vivo. We divided that these mice were randomly assigned to one of five treatment groups for experimental contrast. The antitumor effect was showed with 15-fold higher dose when compared to free gemcitabine. From the result, the magnetic PCL nanoparticles may provide a therapeutic benefit by delivering drugs efficiently to magnetically targeted tumor tissues, thus achieving safe and successful anti-tumor effects with low toxicity.