Cancer cells exposed to heat stress of more than 42.5°C, the inflection point of hyperthermia, undergo cell death ; however, exposure to temperatures below the inflection point induces slight or no cytotoxicity. Due to the complexity of the heat stress signal, the molecular mechanisms involved in cellular responses to heat stress have remained a major challenge to investigations of hyperthermia. Currently the most powerful approaches to elucidating the heat stress response include the use of global-scale microarrays and bioinformatics tools. In this review, we summarize gene expression profiles in the cellular responses to heat stress obtained by these technologies in human lymphoma U937 cells under apoptotic and under non-apoptotic conditions, and we discuss differences in biological functions and gene networks responsive to heat stress between these conditions.

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The soft-heating method induces hyperthermia with elongated heating elements implanted in the body. The element produces heat under high-frequency magnetic field generated by an excitation coil placed outside the body. The element has thermo-sensitive ferrite in a metal loop. Notably, the temperature of the element does not exceed the Curie point, providing an automatic mechanism that limits the heating temperature and enables safe treatment. The heat output of the element depends on magnetic field strength, excitation frequency, and the angle between the element and the incident magnetic field. For example, heating becomes largest when the incident magnetic field is parallel to the long axis of the element. However, the heating area of an element is limited, and multiple elements must be implanted to target a tumor from various angles. Excitation using a solenoid coil or a flat coil is only in one direction, but magnetic field needs to be generated in multiple directions. We use two coils because magnetic field sources in at least two directions allow for a multi-directional magnetic field. It is well known that a current phase difference of 90° between two coils results in a rotating magnetic field. However, induced current might damage the power supply if inductive coupling occurs between the two coils. In addition, a coil without electromagnetic coupling is difficult to apply to the human body. Accordingly, we propose a new method for realizing a multi-directional magnetic field, as well as a clinical coil model. The method uses two excitation frequencies, and a multi-directional magnetic field is obtained at a certain position. Additionally, an important characteristic is that the power supply is safe even if electromagnetic coupling occurs in the coil model. Using this technique, we successfully heated elements placed in various directions.

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Use of hyperthermia as cancer treatment has often been impossible to continue at once following exacerbation of general condition due to cancer growth. However, no formal consensus has yet been defined regarding the acceptability of hyperthermia, so selection of patients for hyperthermia is not based on agreed clinical criteria. Aiming at the establishment of agreed clinical criteria concerning the selection of patients for hyperthermia, this report examined the treatment acceptability of hyperthermia based on patient backgrounds before advanced cancer treatment. Subjects comprised 45 patients with various advanced cancers treated with regional hyperthermia combined with chemo- or immunotherapy who visited our clinic between July 2008 and May 2009. Group A (n=24) underwent hyperthermia ≥ 8 times, while Group B (n=21) underwent hyperthermia ≤ 7 times (mean, 4.19 times). We investigated pretreatment laboratory data, body mass index, performance status (PS), Glasgow prognostic score (GPS), and quality of life (QOL). Patients with poor scores for both PS and GPS dropped out early. In these patients, elevations in both lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels tended to be present in addition to hypoalbuminemia. QOL in Group B was already impaired before initiation of hyperthermia. PS and GPS appear to represent the most important factors when judging the acceptability of hyperthermia, while LDH, CRP, and albumin levels may help such judgments. The acceptability of hyperthermia can be predicted using patient background as evidenced by laboratory data and general conditions, including QOL, before cancer treatment. The results justified further examination in a large number of patients to aim the establishment of agreed clinical criteria concerning the selection of patients for hyperthermia.

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