Heat shock protein (Hsp) 90 is a key regulator of a variety of oncogene products and cell-signaling molecules, and the therapeutic benefit of its inhibition in combination with radiation or chemotherapy has been investigated. In addition, hyperthermia has been used for many years to treat various malignant tumors. We previously described a system in which hyperthermia was induced using thermosensitive ferromagnetic particles (FMP) with a Curie temperature (Tc = 43°C) low enough to mediate automatic temperature control, and demonstrated its antitumor effect in a mouse melanoma model. In the present study, we examined the antitumor effects of combining a Hsp90 inhibitor (geldanamycin; GA) with FMP-mediated hyperthermia. In cultured B16 melanoma cells, GA exerted an antitumor effect by increasing the cells' susceptibility to hyperthermia and reducing expression of Akt. In an in vivo study, melanoma cells were subcutaneously injected into the backs of C57BL/6 mice. FMP were then injected into the resultant tumors, and the mice were divided into four groups: group I, no treatment (control); group II, one hyperthermia treatment; group III, GA alone; and group IV, GA with hyperthermia. When exposed to a magnetic field, the temperature of tissues containing FMP increased and stabilized at the Tc. In group IV, complete regression of tumors was observed in five of nine mice (56%), whereas no tumor regression was seen in groups I-III. Our findings suggest that inhibition of Hsp90 with hyperthermia increases its antitumor effect. Thus, the combination of FMP-mediated, selfregulating hyperthermia with Hsp90 inhibition has important implications for the treatment of cancer. (Cancer Sci 2009; 100: 558-564) H yperthermia is used in the treatment of tumors because tumor cells are more sensitive to temperature in the range of 42-45°C than are normal tissue cells.(1-4) Still higher temperatures (up to 56°C) lead to widespread necrosis, coagulation, or carbonization in a process called 'thermoablation'. Hyperthermia has an advantage over thermoablation in that it has fewer side effects, and its use, alone and in combination with chemotherapy or radiation, in the treatment of a wide variety of malignant tumors has been investigated in both experimental animals and in patients.(5) The most commonly used method of heating in clinical settings is capacitive heating using a radiofrequency electrical field.(4,6,7) The great advantage of capacitive heating is that it is non-invasive. However, this method can cause excessive heating of the fat layer and is not suitable for site-specific hyperthermia because it is difficult to selectively heat only the local tumor region to the intended temperature without also damaging normal tissue. This is because as the electrical field energy is conducted through the normal tissue, it is imperfectly transduced to heat in a manner reflecting the specific rates of absorption by the tissues, which are dependent on their specific electrical properties (e.g. permittivity and resistance).To overcome the disa...
Combining Hsp90/70 inhibition with hyperthermia appears to increase their antitumor effects. Thus, the combination of FMP-mediated, self-regulating hyperthermia with Hsp90/70 inhibition has important implications for cancer treatment.
Hyperthermia has been used for many years to treat a variety of malignant tumors. The Curie temperature (Tc) is a transition point at which magnetic materials lose their magnetic properties, causing a cessation of current and thus heat production. The Tc enables automatic temperature control throughout a tumor as a result of the self-regulating nature of the thermosensitive material. We have developed a method of magnetically-induced hyperthermia using thermosensitive ferromagnetic particles (FMPs) with low Tc (43°°°°C), enough to mediate automatic temperature control. B16 melanoma cells were subcutaneously injected into the backs of C57BL/6 mice, after which tumors were allowed to grow to 5 mm in diameter. FMPs were then injected into the tumors, and the mice were divided into three groups: group I (no hyperthermia, control); group II (one hyperthermia treatment); and group III (hyperthermia twice a week for 4 weeks). When exposed to a magnetic field, the FMPs showed a sharp rise in heat production, reaching the Tc in tissue within 7 min, after which the tissue temperature stabilized at approximately the Tc. In groups I and II, all mice died within 30 -45 days. In group III, however, 6 of 10 mice remained alive 120 days after beginning treatment. Our findings suggest that repeated treatment with magnetically-induced self-regulating hyperthermia, mediated by FMPs with a low Tc, is an effective means of suppressing melanoma growth. A key advantage of this hyperthermia system is that it is minimally invasive, requiring only a single injection for repeated treatments with automatic temperature control. (Cancer Sci 2008; 99: 805-809)
We proposed a quantitative method to calculate water content of thin materials by terahertz (THz) imaging. First, we constructed a THz imaging system using a tunnel injection transit time (TUNNETT) THz wave generator with automatic scanning control. As a suitable imaging spatial resolution is necessary to accurately estimate water content and distribution in samples, we have improved the spatial resolution. Images of plant leaves under different conditions were taken using the THz imaging system. We have introduced an algorithm with the attenuation law of Lambert-Beer to calculate water contents from THz images. To verify the accuracy of this method, we also obtained images of a piece of cotton cloth with different contents of water. Comparison of the calculated values with the measured values obtained using an electronic balance showed that our method has a good possibility for measuring the water content of relatively thin materials by a noncontact and noninvasive method using THz images.
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