Anin VivoStudy of Antifreeze Protein Adjuvant Cryosurgery

Pham, Linda; Dahiya, Rajvir; Rubinsky, Boris

doi:10.1006/cryo.1999.2158

Cited by 82 publications

(35 citation statements)

References 12 publications

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“…One class of proteins for which protein-water interactions are critical to function is antifreeze proteins (AFPs). AFPs are widely distributed in certain plants, vertebrates, fungi, and bacteria to provide cells protection in cold environments [17][18][19][20] but the mechanism for antifreeze activity is still not well understood. In this paper we analyze by all-atom molecular dynamics (MD) simulations the dynamics of water molecules and hydrogen bonds at the protein-water interface of the AFP from the spruce budworm Choristoneura fumiferana and a mutant that has little antifreeze activity.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Water and Hydrogen Bond Dynamics at the Surface of an Antifreeze Protein

Gnanasekaran

Leitner

2012

Journal of Atomic, Molecular, and Optical Physics

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We examine dynamics of water molecules and hydrogen bonds at the water-protein interface of the wild-type antifreeze protein from spruce budworm Choristoneura fumiferana and a mutant that is not antifreeze active by all-atom molecular dynamics simulations. Water dynamics in the hydration layer around the protein is analyzed by calculation of velocity autocorrelation functions and their power spectra, and hydrogen bond time correlation functions are calculated for hydrogen bonds between water molecules and the protein. Both water and hydrogen bond dynamics from subpicosecond to hundred picosecond time scales are sensitive to location on the protein surface and appear correlated with protein function. In particular, hydrogen bond lifetimes are longest for water molecules hydrogen bonded to the ice-binding plane of the wild type, whereas hydrogen bond lifetimes between water and protein atoms on all three planes are similar for the mutant.

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Section: Introductionmentioning

confidence: 99%

Analysis of Water and Hydrogen Bond Dynamics at the Surface of an Antifreeze Protein

Gnanasekaran

Leitner

2012

Journal of Atomic, Molecular, and Optical Physics

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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]. The main hindrance in the clinical use of AFPs is the high concentration (> 5 mg/ml) required to achieve the desired effect.…”

Section: Adjuvants With Cryosurgerymentioning

confidence: 99%

“…Specifically, adjuvants have been identified which can increase the destructive effect of freezing in the −40°C to −0.5°C region such that the kill zone can be raised to −20°C and in some cases extends up to the imaged edge of the iceball (−0.5°C). Identified adjuvants are shown in Table 3 and include anti-freeze proteins, salt solutions, chemotherapeutics such as bleomycin, 5-fluoracil and vascular targeting agents like TNF-α, which enhance the destructive effect of freezing in tissues at temperatures greater than −40°C [35, 37-44]. …”

Section: Introductionmentioning

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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“…69 Other biological response modifi ers, such as antifreeze proteins, may also improve the effi ciency of the freezing process. 70 …”

Section: Multimodal Treatmentmentioning

confidence: 99%