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携载CAⅨ多肽的靶向纳米泡动态监测肾癌移植瘤形成过程的实验研究
Dynamic monitoring of tumor formation in nude mice bearing human renal carcinoma xenograft using targeted nanobubbles carrying CAⅨ polypeptide
- 第三军医大学学报 2018年40卷第8期 页码：652-657
- 作者机构：
400038 重庆，陆军军医大学(第三军医大学)第一附属医院超声科
- 作者简介：
[郭燕丽，E-mail:guoyanli71@aliyun.comGUO Yanli, E-mail:guoyanli71@aliyun.com
- 基金信息：国家国际科技合作专项(2015DFA30920);重庆市国际科技合作专项(CSTC2014gjhz110004);国家自然科学基金面上项目(81771856)
DOI：10.16016/j.1000-5404.201712213
中图分类号： R445.1;R730.41;R737.11收稿：2017-12-05，
修回：2018-02-20，
纸质出版：2018-04-30
- 稿件说明：
移动端阅览
徐丹, 郭燕丽, 朱连华, 等. 携载CAⅨ多肽的靶向纳米泡动态监测肾癌移植瘤形成过程的实验研究[J]. 第三军医大学学报, 2018,40(8):652-657.
Dan XU, Yanli GUO, Lianhua ZHU, et al. Dynamic monitoring of tumor formation in nude mice bearing human renal carcinoma xenograft using targeted nanobubbles carrying CAⅨ polypeptide[J]. Journal of Third Military Medical University, 2018, 40(8): 652-657.
徐丹, 郭燕丽, 朱连华, 等. 携载CAⅨ多肽的靶向纳米泡动态监测肾癌移植瘤形成过程的实验研究[J]. 第三军医大学学报, 2018,40(8):652-657. DOI： 10.16016/j.1000-5404.201712213.
Dan XU, Yanli GUO, Lianhua ZHU, et al. Dynamic monitoring of tumor formation in nude mice bearing human renal carcinoma xenograft using targeted nanobubbles carrying CAⅨ polypeptide[J]. Journal of Third Military Medical University, 2018, 40(8): 652-657. DOI： 10.16016/j.1000-5404.201712213.
摘要
目的
2
应用靶向纳米泡动态监测裸鼠肾癌移植瘤的形成过程，阐明靶向纳米泡在肿瘤形成过程中的成像特征和规律，探索靶向纳米泡诊断微小肿瘤的能力。
方法
2
建立人肾透明细胞癌皮下移植瘤裸鼠模型，于种植后第1天行二维超声检查，于第7天及第14天分别行二维、彩色多普勒血流显像(color doppler flow imaging，CDFI)和超声造影检查，定量分析移植瘤组织和癌旁组织中靶向纳米泡、空白纳米泡和微米泡的显像特点。应用免疫组织化学染色鉴定移植瘤组织和癌旁组织中碳酸酐酶Ⅸ(carbonic anhydrase Ⅸ，CAⅨ)的表达情况。
结果
2
种植后第7天，二维超声和超声造影显示，种植部位形成环状移植瘤组织，中间为未吸收的细胞悬液。种植后第14天，种植部位基本形成实性皮下移植瘤组织，细胞悬液完全吸收。二维超声结合超声造影可发现直径＜1.5 mm的微小肿瘤，且靶向纳米泡在显像峰值强度、峰值降半时间、峰值降半时曲线下面积均优于空白纳米泡和微米泡(
P
<
0.05)，免疫组织化学染色证实移植瘤组织内高表达CAⅨ，而癌旁组织未表达CAⅨ。
结论
2
超声造影能有效监测移植瘤形成的过程，靶向纳米泡能使裸鼠肾癌皮下移植瘤组织特异性显像，有利于肾癌的早期诊断。
Abstract
Objective
2
To monitor the growth of transplanted tumors using ultrasound enhanced by targeted nanobubbles
clarify the ultrasound characteristics of the tumors in nude mice bearing human renal carcinoma xenograft
and explore the potential of targeted nanobubbles in the diagnosis of small tumors.
Methods
2
A nude mouse model bearing subcutaneous xenograft of human clear cell renal cell carcionama (CCRCC) was established. Two-dimensional (2D) ultrasonography was performed on the first day following tumor cell implantation
and 2D
color Doppler flow imaging (CDFI) and contrast-enhanced ultrasound (CEUS) were performed on the 7th and 14th days after the implantation. The ultrasound features of the tumor tissues and adjacent tissues with targeted nanobubbles
blank nanobubbles and microbubbles were quantitatively analyzed. The expression levels of carbonic anhydrase Ⅸ (CAⅨ) in the tumor and adjacent tissues were determined using immunohistochemistry.
Results
2
On day 7 after tumor cell implantation
a ring-like tumor tissue was formed at the implantation site
and the center of the ring contained the cell suspension. Solid tumor was formed at the implantation site on day 14. CEUS was capable of detecting small tumors with a diameter smaller than 1.5 mm
and the peak intensity
half time and area under the curve (AUC) of the half peak intensity of the targeted nanobubbles were all superior to those of blank nanobubbles and microbubbles. Immunohistochemistry confirmed a high expression of CAⅨ in the tumor tissues and no CAⅨ expression in the adjacent tissue.
Conclusion
2
Targeted nanobubbles are capable of specific enhancement of ultrasound imaging of subcutaneously implanted CCRCC xenograft to allow dynamic monitoring of tumor formation and provide assistance in early diagnosis of CCRCC.
关键词
Keywords
references
LAM J S, LEPPERT J T, FIGLIN R A, et al . Role of molecu-lar markers in the diagnosis and therapy of renal cell carcinoma[J ] . Urology, 2005, 66(5): 1-9. DOI: 10.1016/j.urology.2005.06.112.
TOSTAIN J, LI G, GENTIL-PERRET A, et al . Carbonic anhydrase 9 in clear cell renal cell carcinoma: a marker for diagnosis, prognosis and treatment[J ] . Eur J Cancer, 2010, 46(18): 3141-3148. DOI: 10.1016/j.ejca.2010.07.020.
NISHIKAWA M, MIYAKE H, KITAJIMA K, et al . Preoperative differentiation between benign and malignant renal masses smaller than 4 cm treated with partial nephrectomy[J ] . Int J Clin Oncol, 2015, 20(1): 150-155. DOI: 10.1007/s10147-014-0673-7.
IYER A K, KHALED G, FANG J, et al . Exploiting the permeability and retention effect for tumor targeting[J ] . Drug Discovery Today, 2006, 11(17-18): 812-818. DOI: 10.1016/j.drudis.2006.07.005.
FAN X, WANG L, GUO Y, et al . Experimental inv estigation of the penetration of ultrasound nanobubbles in a gastric cancer xenograft[J ] . Nanotechnology, 2013, 24(32): 325102. DOI: 10.1088/0957-4484/24/32/325102.
朱连华, 郭燕丽, 范校周, 等.抗CAⅨ蛋白多糖区多肽的合成及其寻靶能力[J].第三军医大学学报, 2016, 38 (17): 1905-1909. DOI: 10.16016/j.1000-5404.201601172.
ZHU L H, GUO Y L, FAN X Z, et al . Synthesis of anti-CAⅨ proteoglycan-like region peptide and evaluation of its target binding ability[J ] . J Third Mil Med Univ, 2016, 38(17): 1905-1909. DOI: 10.16016/j.1000-5404.201601172.
ZHU L, GUO Y, WANG L, et al . Construction of ultrasonic nanobubbles carrying CAⅨ polypeptides to target carcinoma cells derived from various organs[J ] . J Nanobiotechnol, 2017, 15(1): 63. DOI: 10.1186/s12951-017-0307-0.
FIORI E, DE A C, CROCETTI D, et al . Good results of surgery for renal cell carcinoma depend on early diagnosis. The need for an extensive screening program[J ] . Annali Italiani Di Chirurgia, 2016, 87: 41-44.
戴晴, 姜玉新.超声造影的临床应用[J].中国医学科学院学报, 2008, 30(1): 1-4. DOI: 10.3321/j. issn: 1000-503X. 2008. 01. 001.
DAI Q, JIANG Y X. Clinical applications of contrast-enhanced ultrasound[J]. Acta Acad Med Sine, 2008, 30(1): 1-4. DOI: 10.3321/j.issn: 1000-503X.2008.01.001.
BZYL J, PALMOWSKI M, RIX A, et al . The high angiogenic activity in very early breast cancer enables reliable imaging with VEGFR2-targeted microbubbles (BR55)[J ] . Eur Radiol, 2013, 23(2): 468-475. DOI: 10.1007/s00330-012-2594-z
[TAFRESHI N K, LLOYD M C, BUI M M, et al . Carbonic anhydrase Ⅸ as an imaging and therapeutic target for tumors and metastases[M ] // Carbonic Anhydrase: mechanism, regulation, links to disease, and industrial applications. Springer Netherlands, 2014: 221-254. DOI: 10.1007/978-94-007-7359-2_12. http://dx.doi.org/10.1007/978-94-007-7359-2_12. .
MAHON B P, PINARD M A, MCKENNA R. Targeting carbonic anhydrase Ⅸ activity and expression[J]. Molecules, 2015, 20(2): 2323-2348. DOI: 10.3390/molecules20022323.
KYRIAZIS A P, KYRIAZIS A A, RD M C W, et al . Biological behavior of human malignant tumors grown in the nude mouse[J ] . Cancer Res, 1981, 41(10): 3995-4000.
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