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学科主题: 临床医学
题名:
Liposomal Doxorubicin Increases Radiofrequency Ablation-induced Tumor Destruction by Increasing Cellular Oxidative and Nitrative Stress and Accelerating Apoptotic Pathways
作者: Solazzo, Stephanie A.1; Ahmed, Muneeb1; Schor-Bardach, Rachel1,2; Yang, Wei1,3; Girnun, Geoffrey D.4; Rahmanuddin, Syed1; Levchenko, Tatyana5,6; Signoretti, Sabina7; Spitz, Douglas R.8; Torchilin, Vladimir5,6; Goldberg, S. Nahum1,2
刊名: RADIOLOGY
发表日期: 2010-04-01
DOI: 10.1148/radiol.09091196
卷: 255, 期:1, 页:62-74
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Radiology, Nuclear Medicine & Medical Imaging
研究领域[WOS]: Radiology, Nuclear Medicine & Medical Imaging
关键词[WOS]: HEAT-SHOCK-PROTEIN ; STAGE HEPATOCELLULAR-CARCINOMA ; COLORECTAL LIVER METASTASES ; THERMAL ABLATION ; IN-VIVO ; DRUG ACCUMULATION ; TISSUE ABLATION ; NITRIC-OXIDE ; COAGULATION ; CELLS
英文摘要:

Purpose: To determine if oxidative and nitrative stress and/or apoptosis contribute to increased coagulation when combining radiofrequency (RF) ablation with liposomal doxorubicin.

Materials and Methods: Animal care committee approval was obtained. R3230 mammary adenocarcinomas in Fischer rats were treated with either RF ablation (n = 43), 1 mg of intravenously injected liposomal doxorubicin (n = 26), or combined therapy (n = 30) and were compared with control subjects (n = 11). A subset of animals receiving combination therapy (n = 24) were treated in the presence or absence of N-acetylcysteine (NAC) administered 24 hours and 1 hour before RF ablation. Tumors were analyzed 2 minutes to 72 hours after treatment to determine the temporal range of response by using immunohistochemical staining of the apoptosis marker cleaved caspase-3, phosphorylated g H2AX, and HSP70 and of markers of oxidative and nitrative stress (8-hydroxydeoxyguanosine [8-OHdG], 4-hydroxynonenal [4-HNE]-modified proteins, and nitrotyrosine [NT]). Statistical analyses, including t tests and analysis of variance for comparisons where appropriate, were performed.

Results: By 4 hours after RF ablation alone, a 0.48-mm +/- 0.13 (standard deviation) peripheral band with 57.0% +/- 7.3 cleaved caspase-3 positive cells was noted at the ablation margin, whereas a 0.73-mm +/- 0.18 band with 77.7% +/- 6.3 positivity was seen for combination therapy (P < .03 for both comparisons). Combination therapy caused increased and earlier staining for 4-HNE-modified proteins, 8-OHdG, NT, and g H2AX with colocalization to cleaved caspase-3 staining. A rim of increased HSP70 was identified peripheral to the area of cleaved caspase-3. Parameters of oxidative and nitrative stress were significantly inhibited by NAC 1 hour following RF ablation, resulting in decreased cleaved caspase-3 positivity (0.28-mm +/- 0.09 band of 25.9% +/- 7.4 positivity vs 0.59-mm +/- 0.11 band of 62.9% +/- 6.0 positivity, P < .001 for both comparisons).

Conclusion: Combining RF ablation with liposomal doxorubicin increases cell injury and apoptosis in the zone of increased coagulation by using a mechanism that involves oxidative and nitrative stress that leads to accelerated apoptosis. (C) RSNA, 2010

语种: 英语
所属项目编号: Z0005190040431 ; R01 CA133114 ; R01 CA100045 ; 2R01 HL55519
项目资助者: American Physicians Fellowship for Medicine in Israel ; Beijing Medical Science Technology Commission ; National Institutes of Health
WOS记录号: WOS:000275863000010
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50496
Appears in Collections:北京大学临床肿瘤学院_超声科_期刊论文

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作者单位: 1.Northeastern Univ, Ctr Pharmaceut Biotechnol & Nanomed, Boston, MA 02115 USA
2.Harvard Univ, Sch Med, Lab Minimally Invas Tumor Therapies, Dept Radiol,Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
3.Hadassah Hebrew Univ, Med Ctr, Dept Radiol, Jerusalem, Israel
4.Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst, Dept Ultrasound, Beijing 100871, Peoples R China
5.Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA
6.Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA
7.Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
8.Univ Iowa, Dept Radiat Oncol, Free Radical & Radiat Biol Program, Holden Comprehens Canc Ctr, Iowa City, IA USA

Recommended Citation:
Solazzo, Stephanie A.,Ahmed, Muneeb,Schor-Bardach, Rachel,et al. Liposomal Doxorubicin Increases Radiofrequency Ablation-induced Tumor Destruction by Increasing Cellular Oxidative and Nitrative Stress and Accelerating Apoptotic Pathways[J]. RADIOLOGY,2010,255(1):62-74.
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