[1]刘宇,张福军,兰作平,等.基于兔VX2原位移植肺癌模型评价多西他赛脂质体疗效和安全性[J].第三军医大学学报,2017,39(14):1428-1434.
 LIU Yu,ZHANG Fujun,LAN Zuoping,et al.Efficacy and safety evaluation of docetaxel liposome in a rabbit model bearing orthotopically transplanted VX2 tumor[J].J Third Mil Med Univ,2017,39(14):1428-1434.
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基于兔VX2原位移植肺癌模型评价多西他赛脂质体疗效和安全性(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
39卷
期数:
2017年第14期
页码:
1428-1434
栏目:
基础医学
出版日期:
2017-07-30

文章信息/Info

Title:
Efficacy and safety evaluation of docetaxel liposome in a rabbit model bearing orthotopically transplanted VX2 tumor
作者:
刘宇张福军兰作平张梨王杰余瑜
重庆医科大学:附属第一医院药学部,附属第一医院口腔颌面外科,药学院药物化学与生物材料研究室
Author(s):
LIU Yu ZHANG Fujun LAN Zuoping ZHANG Li WANG Jie YU Yu

Department of Pharmacy, Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016; Department of Pharmaceutical Chemistry and Biological Materials, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China

关键词:
多西他赛脂质体原位移植肺癌模型药效学
Keywords:
docetaxel liposome orthotopic transplantation lung cancer model pharmacodynamics
分类号:
R734.2;R969.4;R979.1
文献标志码:
A
摘要:
目的评价多西他赛脂质体(DTXLP)的远期疗效和不良反应。方法建立兔VX2原位移植肺癌模型,分别静脉给予荷瘤兔空白脂质体(BLALP)、多西他赛注射剂(DTXIN,2.7 mg/kg)、DTXLP高剂量(0.9 mg/kg)、DTXLP中剂量(0.3 mg/kg)以及DTXLP低剂量(0.1 mg/kg)治疗4周期,记录兔生存时间并作生存分析,考察兔存活期间体质量及白细胞计数变化率,食欲减退、腹泻、肠道出血发生率,实验兔死亡后作大体解剖,评估主要脏器的组织病理损害程度。结果BLALP组,DTXIN组,DTXLP高、中、低剂量组兔的中位生存时间分别为28、35、49、34、32 d。生存曲线经LogRank检验,DTXLP高剂量组分别与BLALP组、DTXIN组比较,差异有统计学意义(P=0001,P=0005)。上述各治疗组兔的平均体质量变化率分别为(-23.03±7.99)%、(-11.25±9.67)%、(-1.48±636)%、(-2.08±14.39)%和(-17.27±18.41)%;白细胞计数累积变化率分别为(-3.53±1817)%、(-52.78±12.50)%、(-16.56±10.21)%、(-22.19±10.70)%和(-15.37±14.14)%。DTXIN组和DTXLP高剂量组食欲减退的发生率分别为83.3%和50.0%;BLALP组、DTXIN组及DTXLP高、中、低剂量组腹泻发生率分别为16.7%、66.7%、33.3%、16.7%、16.7%;DTXIN组肠道出血发生率83.3%。病理检查结果显示DTXLP高剂量组的心、肝、脾、肺、肾组织无明显异常,DTXIN组上述脏器均有不同程度的病理损害。结论DTXLP高剂量组明显延长VX2肺癌兔中位生存期,且不良反应轻微。
Abstract:

ObjectiveTo evaluate the longterm efficacy and safety of docetaxel liposome(DTXLP) in a rabbit model of lung cancer. MethodsThirty rabbit models of lung cancer established by orthotopic transplantation of VX2 tumor tissues were randomized in 5 equal groups to receive intravenous injections of blank liposome (BLALP), docetaxel (DTXIN, 2.7 mg/kg), or DTXLP at high (0.9 mg/kg), moderate (0.3 mg/kg) or low (0.1 mg/kg) doses once a week for 4 consecutive weeks, and the survival time of the rabbits was recorded. The survival of the rabbits in each group was estimated using KaplanMeier analysis and analyzed with Logrank test. The changes in body weight and leukocyte count of the rabbits were observed, and the incidence of anorexia, diarrhea and intestinal bleeding were evaluated. After the rabbits died, the heart, liver, spleen, lungs and kidneys were dissected for histopathological examinations. ResultsThe median survival time of the rabbits was 28 d in BLALP group, 35 d in DTXIN group, 49 d in highdose DTXLP group, 34 d in moderatedose DTXLP group and 32 d in lowdose DTXLP group. The survival rate of the rabbits was significantly higher in highdose DTXLP group than in BLALP group (P=0001) and DTXIN group (P=0005). The percent change in the body weight in the 5 groups was (-2303±7.99)%, (-11.25±9.67)%, (-1.48±6.36)%, (-2.08±14.39)% and (-17.27±18.41)%, respectively, and that of leukocyte count was (-3.53±18.17)%, (-52.78±12.50)%, (-16.56±10.21)%, (-22.19±10.70)% and (-15.37±14.14%), respectively. The incidence of anorexia was 83.3% in DTXIN group and 50.0% in highdose DTXLP group. The incidence of diarrhea was 16.7%, 66.7%, 33.3%, 16.7% and 16.7% in the 5 groups, respectively, and intestinal bleeding occurred in DTXIN group was 83.3%. Histological examination revealed obvious pathological changes in the heart, liver, spleen, lungs and kidneys in DTXIN group but not in highdose DTXLP group. ConclusionTreatment with highdose DTXLP significantly prolongs the survival of tumorbearing rabbits with only mild adverse effects.

参考文献/References:

[1]FULTON B, SPENCER C M. Docetaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of metastatic breast cancer[J]. Drugs, 1996, 51(6): 1075-1092.
[2]CHU Q, VINCENT M, LOGAN D, et al. Taxanes as firstline therapy for advanced nonsmall cell lung cancer: a systematic review and practice guideline[J]. Lung Cancer, 2005, 50(3): 355-374. DOI: 10.1016/j.lungcan.2005.06.010.
[3]MONTERO A, FOSSELLA F, HORTOBAGYI G, et al. Docetaxel for treatment of solid tumours: a systematic review of clinical data [J]. Lancet Oncol, 2005, 6(4): 229-239. DOI: 10.1016/S14702045(05)700942.
[4]ZHAO L, WEI Y, LI W, et al. Solid dispersion and effervescent techniques used to prepare docetaxel liposomes for lungtargeted deliver system:in vitro and vivo evaluation[J]. J Drug Target, 2011, 19(3): 171-178. DOI: 10.3109/10611861003801859.
[5]ZHAO L, WEI Y M, ZHONG X D, et al.PK and tissue distribution of docetaxel in rabbits after i.v administration of liposomal and injectable formulation[J]. J Pharm Biomed Anal, 2009, 49(4): 989-996. DOI: 10.1016/j.jpba.2009.01.016.
[6]刘宇, 邱峰, 吕志祥, 等. 99m锝标记多西他赛脂质体的制备及其在兔体内的组织分布研究[J]. 第三军医大学学报, 2016, 38(21): 2303-2308. DOI: 10.16016/j.10005404.201605002.
LIU Y, QIU F, LYU Z X, et al. Preparation of technetium labeled docetaxel liposome and its distribution in rabbits[J]. J Third Mil Med Univ, 2016, 38(21): 2303-2308. DOI: 10.16016/j.1000-5404.201605002.
[7]刘宇, 兰作平, 张福军, 等. 快速微创建立弥漫型兔VX2肺癌模型及其生物学行为研究[J]. 重庆医科大学学报, 2011, 36(9): 1025-1028. 
LIU Y, LAN Z P, ZHANG F J, et al. Study on establishment of rabbit vx2 diffuse lung cancer model with minimally invasive surgery and biological behavior of the tumor[J]. J Chongqing Med Univ, 2011, 36(9): 1025-1028.
[8]KIM G M, KIM M D, KIM DO Y, et al. Transarterial chemoembolization using sorafenib in a rabbit vx2 liver tumor model: pharmacokinetics and antitumor effect[J]. J Vasc Interv Radiol, 2016, 27(7): 1086-1092. DOI: 10.1016/j.jvir.2016.02.032.
[9]MENG M, GAO J, WU C, et al. Doxorubicin nanobubble for combining ultrasonography and targeted chemotherapy of rabbit with VX2 liver tumor[J]. Tumour Biol, 2016, 37(7): 8673-8680. DOI: 10.1007/s1327701545255.
[10]KONDO K, FUJINO H, MIYOSHI T, et al. Orthotopically implanted SCID mouse model of human lung cancer suitable for investigating metastatic potential and anticancer drug effects [J]. Oncol Rep, 2004,12(5): 991-999.
[11]BISSERY M C, NOHYNEK G, SANDERINK G J, et al. Docetaxel (Taxotere): a review of preclinical and clinical experience. Part I: preclinical experience[J]. AntiCancer Drugs, 1995, 6(3): 339-355, 363-368.
[12]KIDD J G, ROUS P. Cancer deriving from the virus papillomas of wild rabbits under natural conditions[J].J Exp Med, 1940, 71(4): 469-494.
[13]BAGULEY B C. Multidrug Resistance in Cancer [J]. Methods Mol Biol, 2010, 596: 1-14.DOI: 10.1007/9781607614166_1.
[14]SZAKáCS G, PATERSON J K, LUDWIG J A, et al. Targeting multidrug resistance in cancer[J]. Nat Rev Drug Discov, 2006, 5(3): 219-234. DOI:10.1038/nrd1984.
[15]ZHOU J, ZHAO W Y, MA X, et al. The anticancer efficacy of paclitaxel liposomes modified with mitochondrial targeting conjugate in resistant lung cancer [J]. Biomaterials, 2013, 34(14):  3626-3638. DOI: 10.1016/j.biomaterials.2013.01.078.
[16]LI X T, ZHOU Z Y, JIANG Y, et al. PEGylated VRB plus quinacrine cationic liposomes for treating nonsmall cell lung cancer[J]. J Drug Target, 2015, 23(3): 232-243. DOI: 10.3109/1061186x.2014.979829.
[17]RAHMAN Y E, HANSON W R, BHARUCHA J, et al. Mechanisms of reduction of antitumor drug toxicity by liposome encapsulation [J]. Ann N Y Acad Sci, 1978, 308: 325-342. DOI: 10.1111/j.17496632.1978.tb22033.x.

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更新日期/Last Update: 2017-07-24