Optimizing heat shock protein expression induced by prostate cancer laser therapy through predictive computational models.
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.
Rylander
Marissa Nichole
MN
Virginia Tech, Department of Mechanical Engineering and School of Biomedical Engineering and Sciences (SBES), Corporate Research Center, Research Building 15 MC 0493, 1880 Pratt Drive, Blacksburg, Virginia 24061, USA. mnr@vt.edu
Feng
Yusheng
Y
Zhang
Yongjie
Y
Bass
Jon
J
Jason Stafford
R
R
Volgin
Andrei
A
Hazle
John D
JD
Diller
Kenneth R
KR
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003198:Computer Simulation; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D017075:Laser Coagulation / Q000379:methods*; D008297:Male; D051379:Mice; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000628:therapy*; D013813:Therapy, Computer-Assisted / Q000379:methods*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins