Chemical adjuvant cryosurgery with antifreeze proteins

Koushafar, Homayoon; Pham, Linda; Lee, C.; Rubinsky, Boris

doi:10.1002/(sici)1096-9098(199710)66:2<114::aid-jso8>3.0.co;2-g

Cited by 77 publications

(38 citation statements)

References 19 publications

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“…apoptosis versus necrosis), cell-based healing responses after freezing/thawing including cell proliferation and migration, and quantitative assessment of ECM structural damage due to freezing. Moreover, the developed model system can be a very useful tool for testing various cryoadjuvants like anti-freeze protein, 16 5-fluorouracil, 7 bleomycin, 20 eutectic forming solutes, 10,11 TNF-alpha 6 which can enhance cryoinjury within a cryolesion and improve the efficacy of cryosurgical technique.…”

Section: Discussionmentioning

confidence: 99%

A Cryoinjury Model Using Engineered Tissue Equivalents for Cryosurgical Applications

et al. 2005

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Cryosurgery is emerging as a promising treatment modality for various cancers, but there are still challenges to be addressed to improve its efficacy. Two primary challenges are determining thermal injury thresholds for various types of cell/tissue, and understanding of the mechanisms of freezing induced cell/tissue injury within a cryolesion. To address these challenges, various model systems ranging from cell suspensions to three-dimensional in vivo tissues have been developed and used. However, these models are either oversimplifications of in vivo tissues or difficult to control and extract precise experimental conditions from. Therefore, a more readily controllable model system with tissue-like characteristics is needed. In this study, a cryoinjury model was developed using tissue engineering technology, and the capabilities of the model were demonstrated. Engineered tissue equivalents (TEs) were constructed by seeding and culturing cells in a type I collagen matrix. Two different cell lines were used in this study, AT-1 rat prostate tumor cells and LNCaP human prostate cancer cells. The constructed TEs underwent a freeze/thaw cycle imitating in vivo cryosurgery. Thermal conditions within TEs during freeze/thaw cycles were characterized, and the responses of TEs to these thermal conditions including freezing induced cellular injury and extracellular matrix damage were investigated at three different time points. The results illustrate the feasibility to establish thermal thresholds of cryoinjury for different cell/tissue types using the presently developed model, and its potential capabilities to study cell death mechanisms, cell proliferation or migration, and extracellular matrix structural damage after a freeze/thaw cycle.

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Section: Discussionmentioning

confidence: 99%

A Cryoinjury Model Using Engineered Tissue Equivalents for Cryosurgical Applications

et al. 2005

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“…Dye uptake analyses were performed after thermal treatment, as described by Koushafar et al 26 ; however, injury was assessed after 3, 24 and 72 h of culture using the method outlined in Rupp et al 27 . In brief, the tumour slices were incubated for 30 min in 1 ml of Dulbecco's phosphate-buffered saline (Invitrogen; Gaithersburg, MD) with 9 mM Hoechst 33342 (Sigma) and 16 mM EthD-1 (Molecular Probes; Eugene, OR).…”

Section: Dye Uptakementioning

confidence: 99%

In vitrothermal therapy of AT-1 Dunning prostate tumours

Bhowmick

Coad

Swanlund

et al. 2004

International Journal of Hyperthermia

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To advance the utility of prostate thermal therapy, this study investigated the thermal thresholds (temperature-time) for prostate tissue destruction in vitro. The AT-1 Dunning prostate tumour model was chosen for the study. Three hundred micron thick sections were subjected to controlled temperature-time heating, which ranged from low (40 degrees C, 15 min) to high thermal exposures (70 degrees C, 2 min) (n = 6). After subsequent tissue culture at 37 degrees C, the sections were evaluated for tissue injury at 3, 24 and 72 h by two independent methods: histology and dye uptake. A graded increase in injury was identified between the low and high thermal exposures. Maximum histologic injury occurred above 70 degrees C, 1 min with >95% of the tissue area undergoing significant cell injury and coagulative necrosis. The control and 40 degrees C, 15 min sections showed histologic evidence of apoptosis following 24 and 72 h in culture. Similar signs of apoptosis were minimal or absent at higher thermal histories. Vital-dye uptake quantitatively confirmed complete cell death after 70 degrees C, 2 min. Using the dye data, Arrhenius analysis showed an apparent breakpoint at 50 degrees C, with activation energies of 135.8 kcal/mole below and 4.7 kcal/mole above the threshold after 3 h in culture. These results can be used as a conservative benchmark for thermal injury in the cancerous prostate. Further characterization of the response to thermal therapy in an animal model and in human tissues will be important in establishing the efficacy of the procedure

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“…AFPs at a very high concentration (>5 mg/ml) have been shown to modify ice crystals to a spicular shape (reducing dendrite tip diameter) such that mechanical disruption of the membranes and tissue connective structures is achieved [43, 44, 82, 83]. Pham et al, showed in an in vivo prostate cancer model that the presence of AFPs can cause injury at temperatures up to −5°C [44].…”

Section: Adjuvants With Cryosurgerymentioning

confidence: 99%

Adjuvant Approaches to Enhance Cryosurgery

Goel

Anderson

Slaton

et al. 2009

Journal of Biomechanical Engineering

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Molecular adjuvants can be used to enhance the natural destructive mechanisms of freezing within tissue. This review discusses their use in the growing field of combinatorial or adjuvant enhanced cryosurgery for a variety of disease conditions. Two important motivations for adjuvant use are: (1) increased control of the local disease in the area of freezing (i.e., reduced local recurrence of disease) and (2) reduced complications due to over-freezing into adjacent tissues (i.e., reduced normal functional tissue destruction near the treatment site). This review starts with a brief overview of cryosurgical technology including probes and cryogens and major mechanisms of cellular, vascular injury and possible immunological effects due to freeze-thaw treatment in vivo. The review then focuses on adjuvants to each of these mechanisms that make the tissue more sensitive to freeze-thaw injury. Four broad classes of adjuvants are discussed including: thermophysical agents (eutectic forming salts and amino acids), chemotherapuetics, vascular agents and immunomodulators. The key issues of selection, timing, dose and delivery of these adjuvants are then elaborated. Finally, work with a particularly promising vascular adjuvant, TNF-alpha, that shows the ability to destroy all cancer within a cryosurgical iceball is highlighted.

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Chemical adjuvant cryosurgery with antifreeze proteins

Cited by 77 publications

References 19 publications

A Cryoinjury Model Using Engineered Tissue Equivalents for Cryosurgical Applications

A Cryoinjury Model Using Engineered Tissue Equivalents for Cryosurgical Applications

In vitrothermal therapy of AT-1 Dunning prostate tumours

Adjuvant Approaches to Enhance Cryosurgery

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