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Development of a tissue engineered human prostate tumor equivalent for use in the evaluation of cryoablative techniques.

Abstract：

:The study of the effectiveness of cryotherapy as a curative treatment for prostate cancer has often relied on the use of either in vitro cell culture monolayers or animal models. While the data gleaned from these studies have been valuable, each model has inherent limitations. In order to bridge the gap between in vitro studies and clinical applications, we developed a 3-dimensional, tissue engineered human prostate cancer model to simulate and assess the effects of cryotherapy and adjunctive treatments on cell viability and activation of cell death pathways throughout the thermally variable freeze zone. Human prostate cancer cells (PC3) were seeded into collagen based matrices and cryolesions were generated using an Oncura SeedNet Gold cryosurgical device with 17-gauge cryoprobes. Analyses revealed widespread necrosis diminishing towards the edge of the freeze zone, and a time-dependent wave of apoptosis starting as early as 1 hr post-thaw at low temperatures (< -40 degrees C) and moving toward the periphery (-20 degrees C) as recovery times reached 12 and 24 hr. Distal to the -10 degrees C isotherm, minimal cell death was apparent (< 20%) over controls. The adjunctive use of chemotherapeutic agents in conjunction with cryosurgery displayed a similar induction of cell death cascades, but with the zone of cryodestruction extending approximately 10 to 15 degrees C further into the freeze zone periphery. By providing an extracellular environment and a matrix to minimize innate variables, the tissue engineered model yielded a more in vivo-like, tumor-like environment supportive of a deeper understanding of the specific biological responses of cancer cells/tumors to cryotherapeutic intervention.

journal_name

Technol Cancer Res Treat

journal_title

Technology in cancer research & treatment

authors

Robilotto AT,Clarke D,Baust JM,Van Buskirk RG,Gage AA,Baust JG

doi

10.1177/153303460700600204

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

81-9

issue

eissn

1533-0346

issn

1533-0338

pii

d=3029&c=4226&p=15802&do=detail

journal_volume

pub_type

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Development of a tissue engineered human prostate tumor equivalent for use in the evaluation of cryoablative techniques.