A model for optimizing adenoviral delivery in human cancer gene therapy trials.

A model for optimizing adenoviral delivery in human cancer gene therapy trials. Research Abstract Details 

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A model for optimizing adenoviral delivery in human cancer gene therapy trials. Abstract Text:

Kenneth N Barton,Svend O Freytag,Teamour Nurushev,Sua Yoo,Mei Lu,Fang-Fang Yin,Shidong Li,Benjamin Movsas,Jae Ho Kim,Stephen L Brown,

Optimization of adenoviral delivery to the target volume is required for adenovirus-mediated cancer gene therapy to reach its maximal potential. The purpose of these studies was to develop a model of gene expression to improve adenovirus-mediated cancer gene therapy in the clinic. We measured the distribution of gene expression after a single deposit of a replication-competent adenovirus carrying the human sodium iodide symporter (hNIS) reporter gene was delivered to naive canine prostate and to human tumor xenografts. We generated hypothetical treatment plans for two prospective prostate cancer patients, using standard brachytherapy algorithms. In both models, the gene expression distribution from a single adenoviral deposit could be accurately described by a Gaussian function. In the naive canine prostate, a 0.1-ml deposit of 3 x 10(11) viral particles (VP) resulted in a gene expression volume of 1.14 +/- 0.70 cm(3), indicating that a minimum of 40 adenoviral deposits would be required to cover a 40-cm(3) prostate with therapeutic gene expression. On a viral particle basis, the gene expression volume obtained in human tumor xenografts (7 x 10(-12) cm(3)/VP) was twice that (3.5 x 10(-12) cm(3)/VP) measured in the naive canine prostate. Hypothetical treatment plans for two prostates indicated that 26 and 57 0.1-ml adenoviral deposits would be required to cover, respectively, 24- and 49-cm(3) prostates with gene expression. Although our studies focused on prostate, we believe the methodology to model gene expression presented here has much broader application to optimize treatment plans in other solid tumor sites; this assertion should be confirmed experimentally.

A model for optimizing adenoviral delivery in human cancer gene therapy trials. Publishing Authors By Initials

KN Barton,SO Freytag,T Nurushev,S Yoo,M Lu,FF Yin,S Li,B Movsas,JH Kim,SL Brown,

For similar surgical procedures, operative: transplantation: transplantation, heterologous research abstracts see: surgical procedures, operative: transplantation: transplantation, heterologous research

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A model for optimizing adenoviral delivery in human cancer gene therapy trials. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Human gene therapy

VOLUME: 18

Page Numbers: 562-72

Journal Abbreviation: Hum. Gene Ther.

ISSN: 1043-0342

DAY: 3

MONTH: Jun

YEAR: 2007

A model for optimizing adenoviral delivery in human cancer gene therapy trials. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9008950

A model for optimizing adenoviral delivery in human cancer gene therapy trials. Keywords Mesh Terms:

KEYWORDS: Transplantation, Heterologous

MESH TERMS: metabolism

Chemical & Substance for Abstract: A model for optimizing adenoviral delivery in human cancer gene therapy trials. Information

Substance Name: sodium-iodide symporter

Registry Number: 0

Grant and Affiliation Information for A model for optimizing adenoviral delivery in human cancer gene therapy trials.

AFFILIATION: Department of Radiation Oncology, Henry Ford Health System, Detroit, MI 48202, USA.

Country: United States

AGENCY: United States NCI

GRANT: P01 CA097012

ACRONYM: CA

MEDLINETA: Hum Gene Ther

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