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诺氏梭菌作为基因载体的靶向性与安全性 被引量:1

TARGET AND SAFETY OF C.NOVYI-NT AS GENE VECTORS
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摘要 目的探讨诺氏梭菌在小鼠乳癌模型体内应用的靶向性和安全性。方法制备小鼠乳癌模型。将减毒诺氏梭菌经尾静脉注射入模型小鼠体内,在注射后的第1、2、4、7天分别处死小鼠,取其肿瘤组织及肝、肾、肺匀浆做厌氧培养,观察减毒诺氏梭菌在小鼠肿瘤组织和各器官中的分布。取注射后第2天瘤体及上述器官制作组织切片,分别用苏木精-伊红及革兰染色,观察瘤体中央坏死区大小及细菌的分布。将减毒诺氏梭菌经尾静脉注射入正常小鼠体内,观察小鼠一般情况及处死后细菌在肝、肾、肺中的分布,评价其在小鼠体内应用的安全性。结果荷瘤小鼠经尾静脉注射减毒诺氏梭菌后,细菌在瘤体中持续大量繁殖;各器官中有少数细菌分布,随时间的延长逐渐减少甚至被全部清除。组织学观察显示实验组小鼠肿瘤中央坏死区大于对照组。正常小鼠注射细菌后一般情况未见异常,7d后各器官培养未见细菌。结论减毒诺氏梭菌对小鼠乳癌具有良好的靶向性,并具有一定的溶瘤作用;其在实验小鼠体内应用有较高的安全性。 Objective To investigate the target and safety of C. novyi-NT used in a mouse model with breast cancer. Methods A breast cancer model in mouse was created. The attenuated C. novyi-NT were injected into the model mice through ve na caudalis, the mice were killed on days l, 2, 4, and 7 after the injection. The tumor tissue and homogenate of liver, kidney and lung were taken for anaerobic culture, the distribution of attenuated C. novyi-NT in tumor tissue and each organ of the mice were observed. The tumors and the above mentioned organs were collected, stained by hematine-eosin or Gram stain, to make histologi- cal sections, the zone of necrosis in tumor centre and distribution of the bacteria were observed. The attenuated C. novyi-NT were injected intravenously into normal mice through vena caudalis. The safety of C. novyi-NT in normal mice was observed that inclu- ded the general condition and bacteria distribution in liver, kidney and lung. The safety of application of attenuated C. novyi-NT in the mouse was valuated. Results A great number of C. novyi-NT to multiply in the tumor after injection of attenuated C. novyi- NT, and a few of becteria were seen in each organ, which were decreased along with the extension of time, and even cleared. His- tologically, the zone of necrosis in the centre of the tumor was larger than that in the normal control. In normal mice, the general condition was not changed after injection of the bacteria, and the result after seven-day bacterial culture of each organ was negative. Conclusion Attenuated C. novyi-NT has a favourable target toward the mice with breast cancer, and with a certan oncolysis, which has a relative safety in experimental mice.
出处 《青岛大学医学院学报》 CAS 2012年第4期327-329,333,共4页 Acta Academiae Medicinae Qingdao Universitatis
关键词 梭菌属 基因疗法 肿瘤靶向性 安全 Clostridium gene therapy tumor targeting safety
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  • 1PATYAR S, JOSHI R, BYRAV D S P, et al. Review bacteria in cancer therapy: a novel experimental strategy[J]. J Biomed Sci, 2010,17(1) :21-30.
  • 2LEMMON M J, VAN ZIJL P, FOX M E, et al. Anaerobic bacteria as a gene delivery system that is controlled by the tumor microenvironment[J]. Gene Therapy, 1997,4( 8):791- 796.
  • 3王晨飞,王凤寰,田平芳,谭天伟.丙酸梭菌简易培养及电转化方法[J].生物加工过程,2010,8(5):35-38. 被引量:2
  • 4LI Z, FALLON J, MANDELI J, et al. A genetically cnhanced anaerobic bacterium for oncopathic therapy of pancreatic cancer[J]. JNCI Journal of the National Cancer Institute 2008,100(19):1389-1400.
  • 5EL-ANEED A. An overview of current delivery systems in cancer gene therapy[J]. Journal of Controlled Release, 2004, 94(1):1-14.
  • 6庞凤.用于肿瘤基因治疗的慢病毒载体研究进展[J].青岛大学医学院学报,2009,45(5):493-494. 被引量:4
  • 7王衍刚,窦以河,刘世海,姚如永,隋爱华,刘相萍.重组分泌型TRAIL腺病毒载体的构建及鉴定[J].齐鲁医学杂志,2011,26(6):494-496. 被引量:3
  • 8JIA W, ZHOU Q. Viral vectors for cancer gene therapy: viral dissemination and tumor targeting[J]. Current Gene Therapy, 2005,5(1):133-142.
  • 9TOSO J F, GILI. V J, HWU P, et al. Phase Ⅰ study of the intravenous administration of attenuated salmonella typhimurium to patients with metastatic melanoma[J]. J Clin Oneol, 2002, 20(1):142-152.
  • 10PARKER R C, PI.UMMER H C. Effect of histolyticus infection and toxin on transplantable mouse tumors[J]. Proc Soc Exp Biol Med, 1947,66(2):461-467.

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  • 1DANG L H, BETTEGOWDA C,HUSO D L, et al. Combination bacteriolytic therapy for the treatment of experimental tumors E J. Proc Natl Aead Sci USA, 2001,98(26) :15155-15160.
  • 2WEI M Q, ELLEM K A, DUNN P, et al. Facultative or ob- ligate anaerobic bacteria have the potential for multimodality therapy of solid tumours[J]. Eur J Cancer, 2007,43 (3) : 490 496.
  • 3LIU S C, MINTON N P, GIACCIA A J, et al. Anticancer ef- ficacy of systemically delivered anaerobic bacteria as gene the- rapy vectors targeting tumor hypoxia/necrosis[J]. Gene Ther, 2002,9 (4) 291-296.
  • 4THEYS J, PENNINGTON O, DUBOIS L, et al. Repeated cycles of clostridium-directed enzyme prodrug therapy result in sustained antitumour effects in vivo[J]. Br J Cancer, 2006,95(9)1212-1219.
  • 5LIU S C, AHN G O, KIOI M, et al. Optimized clostridia-di- rected enzyme prodrug therapy improves the antitumor activity of the novel DNA-cross-linking agent PR-104[J]. Cancer Res, 2008,68(19) :7995-8003.
  • 6张清华,王言奎.宫颈癌组织HIF-1α和IGF-2表达及意义[J].齐鲁医学杂志,2011,26(1):8-10. 被引量:7
  • 7张艳丽,张文卿,王秋波,丁守怡,吕锐,董海.hIL-12及HER2/neu ECD修饰的生孢梭菌工程菌的构建及鉴定[J].免疫学杂志,2011,27(11):987-991. 被引量:2

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