GENE THERAPY OF CARCINOMA USING ULTRASOUND-TARGETED MICROBUBBLE DESTRUCTION

被引：77

作者：

Carson, Andrew R. ^{[1
]}

McTiernan, Charles F. ^{[1
]}

Lavery, Linda ^{[1
]}

Hodnick, Abigail ^{[1
]}

Grata, Michelle ^{[1
]}

Leng, Xiaoping ^{[1
]}

Wang, Jianjun ^{[1
]}

Chen, Xucai ^{[1
]}

Modzelewski, Ruth A. ^{[2
]}

Villanueva, Flordeliza S. ^{[1
]}

机构：

[1] Univ Pittsburgh, Med Ctr, Ctr Ultrasound Mol Imaging & Therapeut, Cardiovasc Inst, Pittsburgh, PA 15213 USA

[2] Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA 15213 USA

来源：

ULTRASOUND IN MEDICINE AND BIOLOGY | 2011年 / 37卷 / 03期

基金：

美国国家卫生研究院;

关键词：

Nonviral vectors; Ultrasound contrast agents; Ultrasound imaging; Targeting strategies; Squamous cell carcinoma; Suicide genes; MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; RED-BLOOD-CELLS; IN-VIVO; THYMIDINE KINASE; GLIOBLASTOMA-MULTIFORME; PANCREATIC-ISLETS; DELIVERY; SONOPORATION; EXPRESSION; CANCER;

D O I：

10.1016/j.ultrasmedbio.2010.11.011

中图分类号：

O42 [声学];

学科分类号：

070206 ; 082403 ;

摘要：

When microbubble contrast agents are loaded with genes and systemically injected, ultrasound-targeted microbubble destruction (UTMD) facilitates focused delivery of genes to target tissues. A mouse model of squamous cell carcinoma was used to test the hypothesis that UTMD would specifically transduce tumor tissue and slow tumor growth when treated with herpes simplex virus thymidine kinase (TK) and ganciclovir. UTMD-mediated delivery of reporter genes resulted in tumor expression of luciferase and green fluorescent protein (GFP) in perivascular areas and individual tumor cells that exceeded expression in control tumors (p = 0.02). The doubling time of TK-treated tumors was longer than GFP-treated tumors (p = 0.02), and TK-treated tumors displayed increased apoptosis (p = 0.04) and more areas of cellular drop-out (p = 0.03). These data indicate that UTMD gene therapy can transduce solid tumors and mediate a therapeutic effect. UTMD is a promising nonviral method for targeting gene therapy that may be useful in a spectrum of tumors. (E-mail: villanuevafs@upmc.edu) (C) 2011 World Federation for Ultrasound in Medicine & Biology.

引用

页码：393 / 402

页数：10

共 38 条

[21] Myocardial contrast echocardiography - A 25-year retrospective [J].

Kaul, Sanjiv .

CIRCULATION, 2008, 118 (03) :291-308

[22] Optimising ultrasound-mediated gene transfer (sonoporation) in vitro and prolonged expression of a transgene in vivo: Potential applications for gene therapy of cancer [J].

Li, Ying Suet ;

Davidson, Emma ;

Reid, Cherith N. ;

McHale, Anthony P. .

CANCER LETTERS, 2009, 273 (01) :62-69

[23] Targeted drug delivery system for oral cancer therapy using sonoporation [J].

Maeda, Hironobu ;

Tominaga, Kazuhiro ;

Iwanaga, Kenjiro ;

Nagao, Fuminori ;

Habu, Manabu ;

Tsujisawa, Toshiyuki ;

Seta, Yuji ;

Toyoshima, Kuniaki ;

Fukuda, Jin-ichi ;

Nishihara, Tatsuji .

JOURNAL OF ORAL PATHOLOGY & MEDICINE, 2009, 38 (07) :572-579

[24] Ultrasound and Microbubble-Targeted Delivery of Macromolecules Is Regulated by Induction of Endocytosis and Pore Formation [J].

Meijering, Bernadet D. M. ;

Juffermans, Lynda J. M. ;

van Wamel, Annemieke ;

Henning, Rob H. ;

Zuhorn, Inge S. ;

Emmer, Marcia ;

Versteilen, Amanda M. G. ;

Paulus, Walter J. ;

van Gilst, Wiek H. ;

Kooiman, Klazina ;

de Jong, Nico ;

Musters, Rene J. P. ;

Deelman, Leo E. ;

Kamp, Otto .

CIRCULATION RESEARCH, 2009, 104 (05) :679-U226

[25] Progress and prospects: immune responses to viral vectors [J].

Nayak, S. ;

Herzog, R. W. .

GENE THERAPY, 2010, 17 (03) :295-304

[26]

Nie F, 2008, J DRUG TARGET, V16, P389, DOI [10.1080/10611860802088846, 10.1080/10611860802088846 ]

[27] PET imaging of heat-inducible suicide gene expression in mice bearing head and neck squamous cell carcinoma xenografts [J].

Parry, J. J. ;

Sharma, V. ;

Andrews, R. ;

Moros, E. G. ;

Piwnica-Worms, D. ;

Rogers, B. E. .

CANCER GENE THERAPY, 2009, 16 (02) :161-170

[28] Delivery of colloidal, particles and red blood cells to tissue through microvessel ruptures created by targeted microbubble destruction with ultrasound [J].

Price, RJ ;

Skyba, DM ;

Kaul, S ;

Skalak, TC .

CIRCULATION, 1998, 98 (13) :1264-1267

[29] A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme [J].

Rainov, NG .

HUMAN GENE THERAPY, 2000, 11 (17) :2389-2401

[30]

REINHOLD HS, 1983, INT J MICROCIRC, V2, P143

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