Optimizing heat shock protein expression induced by prostate cancer laser therapy through predictive computational models

Abstract

Thermal therapy efficacy can be diminished due to heat shock protein (HSP) induction in regions of a tumor where temperatures are insufficient to coagulate proteins. HSP expression enhances tumor cell viability and imparts resistance to chemotherapy and radiation treatments, which are generally employed in conjunction with hyperthermia. Therefore, an understanding of the thermally induced HSP expression within the targeted tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of the overall tissue response. A treatment planning computational model capable of predicting the temperature, HSP27 and HSP70 expression, and damage fraction distributions associated with laser heating in healthy prostate tissue and tumors is presented. Measured thermally induced HSP27 and HSP70 expression kinetics and injury data for normal and cancerous prostate cells and prostate tumors are employed to create the first HSP expression predictive model and formulate an Arrhenius damage model. The correlation coefficients between measured and model predicted temperature, HSP27, and HSP70 were 0.98, 0.99, and 0.99, respectively, confirming the accuracy of the model. Utilization of the treatment planning model in the design of prostate cancer thermal therapies can enable optimization of the treatment outcome by controlling HSP expression and injury.

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“…The diffusion equation was used to investigate the imaging depth in tissue imaging. The detailed parameters and boundary conditions settings involved in these models were determined according to tissue optics, heat transfer and biological damage [11,12,[22][23][24][25][26].…”

Using Cyber-Infrastructure for Dynamic Data Driven Laser Treatment of Cancer

“…P is the laser power, μ a , μ s are laser coefficients related to laser wavelength and give probability of absorption of photons by tissue, γ is the anisotropy factor, and x 0 is the position of laser photon source. Constitutive model data and details of the optimization process are given in [8,11].…”

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“…Cellular damage is measured in terms of the damage fraction F D predicted by means of an Arrhenius integral formulation [6].…”

“…2, was created by a semiautomatic segmentation method adapted to find the interface boundaries of tumor and tissue. Cubic spline and lofting methods are applied to obtain smooth boundaries from the segmented MRI data [6,7].…”

“…This is due, in part, to the expression of HSP in the regions of thermal stress. Consequently, knowledge of the thermal dose necessary to activate or deactivate HSP expression as a function of temperature and time in the affected tissue [6,8] can be critical in planning and implementing an effective thermal treatment by laser surgery.…”