Hyperthermia is a method by which external heat is applied to eliminate or control the growth of tumor cells and tissue by causing a raise in their temperature. However, existing knowledge is largely based on the temperature of the extracellular environment and little is known about intracellular temperatures. Recently, the invention of multiple new fluorescent thermometers has enabled the measurement of intracellular temperatures at high spatial resolution, hence facilitating the discussion of cellular activity from a thermodynamic point of view. This review focuses on fluorescent thermometers among the technologies developed for measuring intracellular temperatures, specifically providing a detailed account of recent findings regarding fluorescent polymer thermometers (FPTs). FPTs are capable of highly precise temperature measurements, to the order of 0.1°C in a single cell. They have been used to reveal that intracellular temperatures are not uniform; for instance, the temperature of the nucleus is found to be higher than that of other cell organelles. It is expected that progress in the development of intracellular temperature measurement techniques, including FPTs, will provide a better understanding of hyperthermia, thus making it a more versatile and effective treatment method.
Cancer stem cells (CSCs) or tumor-initiating cells (TICs) have been identified in a variety of cancers and are defined as a small population of cancer cells that have stem cell-like phenotypes. CSCs are resistant to current chemotherapy and radiotherapy and have high ability of tumorigenesis. It is likely that CSCs contribute to cancer metastases and tumor recurrence, which cause a poor prognosis. Thus, targeting strategy of CSCs is extremely important for advancement of cancer therapies. However, CSC itself is not well understood. This review refers to key points to be noticed in CSC research and considers effectiveness of hyperthermia for CSC-targeting. It has been reported that heating has an inhibitory influence on some extra- and intra-cellular factors that are related to the survival of CSCs. In this review, the potentiality of hyperthermia for CSC-targeted cancer therapy is discussed with relation to those survival factors.
This study was undertaken to evaluate the tumor response to magnetic hyperthermia treatment (MHT) combined with cisplatin (MHT+CDDP) using magnetic particle imaging (MPI). Colon-26 cells were implanted into the backs of mice. When the tumor volume exceeded approximately 100 mm3, the mice were divided into control, MHT, CDDP, and MHT+CDDP groups. In the CDDP and MHT+CDDP groups, CDDP (5 mg/kg) was injected intraperitoneally. In the MHT+CDDP group, magnetic nanoparticles[250 mM (14.0 mg Fe/mL) Resovist®]were directly injected into the tumor one hour after CDDP administration, and MHT was performed for 20 min using an alternating magnetic field. In the MHT group, only MHT was performed after the injection of Resovist®. In the MHT+CDDP and MHT groups, MPI images were obtained using our MPI scanner immediately before, immediately after, and 3, 7, and 14 days after MHT. After the MPI studies, we drew a region of interest (ROI) on the tumor in the MPI image and calculated the average and maximum MPI values and the number of pixels within the ROI. In all groups, the relative tumor volume growth (RTVG) was calculated from (V-V0)/V0, where V0 and V were the tumor volumes immediately before and after treatment, respectively. The RTVG value in the MHT+CDDP group was significantly lower than that in the MHT group 3 to 14 days after MHT. It was also significantly lower than that in the CDDP group at 4 to 11 days except at 6 and 9 days after treatment. The average and maximum MPI values normalized by those immediately before MHT in the MHT+CDDP group were significantly higher than those in the MHT group 3 days after MHT. Our results suggested that MPI is useful for quantitatively evaluating tumor response to MHT combined with chemotherapy.
Combination of interstitial hyperthermia and radiation brachytherapy has been shown to be effective for treatment of a tumor. After increasing the temperature, the tumor becomes sensitive to radiation dose, and as a result the radiation dose can be reduced. The purpose of this study was to identify the appropriate invasive antenna array which can be effectively used on a deep-seated breast tumor to increase the temperature to more than 42.5°C, and to examine the effect of a smaller cumulative radiation dose of 30 Gy. We have found coaxial-slot antenna array to be the most appropriate for applying hyperthermia on a deep-seated breast tumor. The temperature distributions were measured with a breast phantom, and specific absorption rate (SAR) distributions were calculated using a simulation software. A coaxial-slot antenna array, consisting of two coaxial-slot antennas, separated by 5 mm, and using a microwave power of 15 W increased the temperature of a tumor phantom, in an area of 30 mm in diameter, to over 42.5°C in 30 min. The temperature as well as SAR were observed to have increased more in the tumor tissue than in the other types of tissues which were tested. Thereafter, we have examined the radiation dose distribution of brachytherapy using a treatment planning software. Simulations were conducted on the Computed Tomography image of an anonymous breast tumor patient; the tumor's dimensions were 40 mm (length)×30 mm (width). A radiation dose of 30 Gy given in 5 fractions of 6 Gy each, which is lesser than the conventional radiation doses used in external beam radiation therapy, was applied to the tumor. Harm to adjacent tissues is also expected to be minimized due to lower radiation dose. As a result of this study, there is a possibility of local control of deep-seated small breast tumors using a combination of interstitial hyperthermia by using coaxial-slot antenna array to increase the temperature to over 42.5°C and radiation brachytherapy by applying cumulative dose of 30 Gy.
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