Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone protein. The Hsp90 superchaperone complex assists folding and function of a variety of client proteins. Many oncoproteins are Hsp90 client proteins. Compared to normal cells, tumor cells require higher Hsp90 chaperone activity ; therefore, targeting Hsp90 with chemical inhibitors disrupts multiple oncogenic processes and has potent antitumor activity. Many Hsp90 inhibitors are currently being tested in preclinical or clinical trials. This review summarizes published data concerning radiosensitization of human tumor cells in in vitro and in vivo tumor models with Hsp90 inhibitors.

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Hyperthermia (HT) has been considered a promising approach in cancer therapy. However, the acquisition of thermoresistance in tumor due to several responses of tumor, such as an increase in heat shock proteins (HSPs), makes HT less effective. The induction of HSPs is mainly mediated by the activation of heat shock transcription factor 1 (HSF1). It has been shown that HSF1 is abundantly expressed in human tumor cells of various origins. Moreover, it takes part in the initiation and maintenance of tumor. Silencing of HSF1 could suppress tumor formation and enhance the effectiveness of HT. In this review, the physiological and pathological roles of HSF1 in cancer cells are summarized, and its potential as a therapeutic target for hyperthermic therapy is discussed.

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Heat shock protein A (HSPA) family members consist of at least 13 genes. We studied the effects of heat stress on the gene expression of HSPA family members in normal human fibroblastic (NHF) cells. Four NHF cell lines, Hs68, OUMS-36, NTI-4, and KD, were treated with mild hyperthermia (MHT) at 41°C for 30 min or hyperthermia (HT) at 43°C for 30 min, followed by culturing for 1 or 24 h at 37°C. Treatment of cells with HT significantly induced cell death, whereas this change was not observed in cells treated with MHT. Real-time quantitative polymerase chain reaction demonstrated that the expression levels of HSPA1A, HSPA1B, HSPA1L, HSPA4, HSPA4L, HSPA5 and HSPA6 were significantly elevated in the cells treated with MHT and HT, and the HT treatment was more effective than the MHT treatment. This report is the first to describe an increase in HSPA4 expression by heat treatment. These alterations were observed in all four NHF cell lines in the same way. On the other hand, neither MHT nor HT affected the expression levels of HSPA2, HSPA8, HSPA9, HSPA12A, HSPA13 and HSPA14. These results demonstrated that HSPA1A, HSPA1B, HSPA1L, HSPA4, HSPA4L, HSPA5 and HSPA6 were heat-inducible HSPA genes, but the remaining HSPA family members were constitutive (not heat-inducible) HSPA genes. Under the non-heated condition at 37°C, the expression levels of constitutive HSPA genes were higher than those of heat-inducible HSPA genes. In conclusion, the gene expression patterns of HSPA family members responsive to heat stresses in NHF cells were identified. These results may provide a basis for understanding the molecular mechanisms of MHT and HT in normal cells.

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A noninvasive magnetic resonance temperature imaging technique for fat-water mixed tissues was proposed. This technique uses the temperature dependence of the spin-lattice relaxation time (T₁) of protons originated from methylene chain (CH₂) of fat as well as the resonance frequency shift of water proton (H₂O). A multiple point Dixon method in conjunction with a multiple flip angle method enables simultaneous calculation of T₁ of CH₂ and the resonance frequency change of H₂O. A phantom with two mayonnaise tubes, one heated by microwave while the other kept at room temperature was imaged at 3 Tesla during the cooling process by a spoiled gradient recalled acquisition in steady state (SPGR) of the following conditions ; field of view, 32×32 cm² ; matrix, 64×64 ; parallel imaging factor, 2 ; repetition time, 36 ms ; echo time spacing, 1.15 ms ; and flip angles, 20, 50 and 70 degrees. Signals obtained with each flip angle were processed by IDEAL (Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation) algorithm to obtain H₂O, CH₂ and CH₃ images. The smaller components of fat were ignored for simplicity. Temperature distribution of fat in the phantom was imaged by T₁ of CH₂ obtained from the three CH₂ images with different flip angles, while that of water with the change in the phase difference between H₂O and CH₂ or the relative phase change in H₂O. Those temperature images were then fused as a weighted sum of H₂O and CH₂ fractions in each voxel. The resultant images highly correlated with the probe-measured temperature elevation demonstrating that simultaneous fat-water temperature imaging is feasible and is expected to be sufficient for clinical practice.

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