Heat shock protein response in a prostate tumor model to interstitial thermotherapy: Implications for clinical treatment

Abstract

Hyperthermia is being utilized individually and in conjunction with other therapies in treating malignant and benign tumors, though few studies have examined cellular effects of elevated temperatures in the prostate model. Highly conserved proteins of the 70 kDa heat shock protein family (HSP 70) are produced in response to environmental stresses, including heat, and are found in all organisms. HSPs are an indicator of cell damage, are associated with thermotolerance, and provide cells with transient resistance to subsequent thermal challenges. Transient thermotolerance is important in the determination of temperature, duration, and sequencing for treatments. This preliminary study analyzes the HSP 70 response of the Dunning R3327 adenocarcinoma model to a single 50 degrees C 1 hr treatment. Elevated HSP levels were found between 10 and 16 hr, returning to baseline by 24 hr. As some fractions of the cells are able to produce HSP 70 following treatment, the data suggest that currently utilized clinical temperatures (42-46 degrees C) administered for 1 hr are inadequate. HSP levels in response to hyperthermia, radiation, and chemotherapy may be useful in finding optimal treatment regimens for prostate cancer.

Improved therapeutic response by distinct timing of multiple heat treatments during interstitial radiation in the Dunning R3327 prostate tumor model

“…This holds not only for the application of multiple treatments (1±7 within 12 days) at 43.5°C for 35 min but also for dierent doses of heat produced by either varying the temperature applied (42.5±44.5°C) or the time (20±65 min). These results are supported by interstitial hyperthermia studies in the R3327 tumor model where only heat doses of 50°C for 1 h produced a measurable sign of cellular response (Paulus et al 1993). This lack of response to heat has not only greatly simpli®ed the analysis and interpretation of our results, but also clearly shown that radiosensitization is the dominant eect during LTH combined with IR in our tumor system, presumably because of impaired repair of radiation-induced DNA lesions (Dikomey and Jung 1993;Kampinga 1993).…”

Overexpression of human 27 kDa heat shock protein in laryngeal cancer cells confers chemoresistance associated with cell growth delay

“…Furthermore, several studies have demonstrated that the expression of HSP27 is increased in various human cancers, suggesting that the cytoprotective activity of HSP27 might aVect tumorigenesis and the susceptibility of tumors to cancer treatment (Richards et al 1996;Vargas-Roig et al 1998;Fortin et al 2000). Supporting this postulation, HSP27 expression was reported to be correlated with a poor prognosis after surgery or a resistance to adjuvant therapy in many types of cancers including gastric cancer, breast cancer, osteosarcoma, and prostate carcinoma (Paulus et al 1993;Nakopoulou et al 1995;Liu et al 1996;Uozaki et al 1997). In head and neck cancers, HSP27 has been frequently shown to be expressed at high levels in squamous cell carcinomas over the oral cavity, the orophyarynx and larynx, as well as in normal upper respiratory tract mucosa (Sugerman et al 1995;Gandour-Edwards et al 1998).…”

Effects of combined treatment of chemotherapeutics and hyperthermia on survival and the regulation of heat shock proteins in dunning R3327 prostate carcinoma cells

“…In vitro experiments, in vivo animal studies, and clinical trials have revealed that hyperthermia may serve as a powerful tool in the treatment of prostate cancer [6][7][8][9][10]. At the cellular level, hyperthermic stress induces the synthesis of a class of proteins termed ''heat shock proteins'' (HSP).…”