Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method c...Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method called magnetic particle imaging (MPI) has been introduced. MPI allows imaging of the spatial distribution of MNPs. The purpose of this study was to investigate the feasibility of visualizing and quantifying the intratumoral distribution and temporal change of MNPs and predicting the therapeutic effect of MHT using MPI. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, mice were divided into untreated (n = 10) and treated groups (n = 27). The tumors in the treated group were directly injected with MNPs (Resovist?) with iron concentrations of 500 mM (A, n = 9), 400 mM (B, n = 8), and 250 mM (C, n = 10), respectively, and MHT was performed using an AMF with a frequency of 600 kHz and a peak amplitude of 3.5 kA/m. The mice in the treated group were scanned using our MPI scanner immediately before, immediately after, 7 days, and 14 days after MHT. We drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels by taking the threshold value for extracting the contour as 40% of the maximum MPI value (pixel value) within the ROI. These parameters in the untreated group were taken as zero. We also measured the relative tumor volume growth (RTVG) defined by (V-V0)/V0, where V0 and V are the tumor volumes immediately before and after MHT, respectively. Results: The average, maximum, and total MPI values decreased up to 7 days after MHT and remained almost constant thereafter in all groups, whereas the number of pixels tended to increase with time. The RTVG values in Groups A and B were significantly lower than those in the control group 3 days or more and 5 days or more after MHT, respectively. The above four parameters were significantly inversely correlated with the RTVG values 5, 7, and 14 days after MHT. Conclusion: MPI can visualize and quantify the intratumoral distribution and temporal change of MNPs before and after MHT. Our results suggest that MPI will be useful for predicting the therapeutic effect of MHT and for the treatment planning of MHT.展开更多
Physicians often observe patients’ complexion (their natural skin color) as an indicator of health. The complexion may depend on the internal environment, however, very few researchers studied its evidence. We previo...Physicians often observe patients’ complexion (their natural skin color) as an indicator of health. The complexion may depend on the internal environment, however, very few researchers studied its evidence. We previously reported various benefits of a mild hyperthermia treatment on human health using the nano-mist sauna (NMS), including acceleration of gas exchange (O2 and CO2) in the venous blood, enhancement of immunity, and the modulation of autonomic nervous system. However, the effects of NMS on skin appearance are unknown. There is a historical and widespread belief that mild hyperthermic treatments such as hot springs are good for improving skin appearance. However, the effect of NMS on the skin appearance has not been examined. In the present study, we examined the color of venous blood using the CIELAB (a color space specified by the French Commission internationale de l’éclairage) method, and then compared the color changes before and after NMS stimulation. Next, we examined correlations of blood gas parameters with color elements of the venous blood, which are highly dependent on oxygen. Our results suggest that the colors and appearance of the face depend on the internal environment, because there are numerous vessels under the skin. Thus, the color of the venous blood may provide medical evidence of changes in complexion. This new method may be useful for assessment of medical complexion by physicians, for use in determining internal health based on skin color information.展开更多
Cancer patients with bone metastases in their extremities may require surgical intervention to prevent deterioration in their quality of life due to a pathological fracture or severe bone pain. However, curative surgi...Cancer patients with bone metastases in their extremities may require surgical intervention to prevent deterioration in their quality of life due to a pathological fracture or severe bone pain. However, curative surgical interventions sometimes have severe complications due to the status of the original cancers. To avoid the decreased quality of life caused by bone metastasis, minimally invasive surgery that avoids additional surgical morbidity is required. We have established two therapeutic treatments for bone metastasis, a photodynamic acridine orange treatment (AOT) and an electronic magnetic hyperthermia treatment (EMHT). The present study investigated the clinical outcomes of combination therapy with EMHT and AOT for patients with bone metastases in their extremities. Methods: The study included 6 patients with 7 bone cancer metastasis locations. For bone metastases, all patients received intraregional tumor excision supported by AOT, in which photodynamic and radiodynamic therapy kills tumor cells during surgery with minimal damage to normal tissues. After the curettage, bone reconstruction was performed by using magnetic materials with calcium phosphate cement. EMHT was repeatedly performed after surgery. In EMHT, tumor cells are killed with an electric magnetic field generator, and bony union is promoted by electronic stimulation. Results: The mean duration of follow-up was 14 months. During the follow-up period, only one patient experienced a local recurrence, and this recurrence occurred 14 months after surgery. Bony union occurred in 4 of 5 cases (80%), and the pain score was significantly reduced after surgery. Conclusions: In the present study, AOT reduced the invasiveness of surgery. EMHT reduced the tumor growth without major complications and promoted bone formation after surgery. Our clinical results confirmed that EMHT and AOT combination therapy for bone metastasis can preserve limb function without local recurrence or bone absorption.展开更多
The purpose of this study was to evaluate the effectiveness of intracellular magnetic hyperthermia treatment (MHT) in comparison with that of extracellular MHT using magnetic particle imaging (MPI). Colon-26 cells wer...The purpose of this study was to evaluate the effectiveness of intracellular magnetic hyperthermia treatment (MHT) in comparison with that of extracellular MHT using magnetic particle imaging (MPI). Colon-26 cells were implanted subcutaneously into the backs of 8-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, the mice were divided into control (n = 10), extracellular MHT (n = 8), and intracellular MHT groups (n = 7). In the control group, MHT was not performed. In the extracellular MHT and intracellular MHT groups, the tumors were injected directly with magnetic nanoparticles (MNPs) (400 mM Resovist®) and were heated for 20 min using an alternating magnetic field. During MHT, the temperatures of the tumor and rectum were measured using optical fiber thermometers. In the extracellular MHT group, MHT was performed 15 min after the injection of MNPs, whereas MHT was performed one day after the injection of MNPs in the intracellular MHT group. In both groups, MPI images were obtained using our MPI scanner immediately before, immediately after, and 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, maximum, and total MPI values and the number of pixels within the ROI. Transmission electron microscopic (TEM) images were also obtained from resected tumors. In all groups, tumor volume was measured every day and the relative tumor volume growth (RTVG) was calculated. The TEM images showed that almost all the MNPs were aggregated in the extracellular space in the extracellular MHT group, whereas they were contained within the intracellular space in the intracellular MHT group. Although the temperature of the tumor in the intracellular MHT group was significantly lower than that in the extracellular MHT group, the RTVG value in the intracellular MHT group was significantly lower than that in the control group 2 days or more after MHT and that in the extracellular MHT group 3, 4, and 5 days after MHT. The average MPI value normalized by that immediately before MHT in the intracellular MHT group was significantly higher than that in the extracellular MHT group immediately and 7 days after MHT. The maximum and total MPI values normalized by those immediately before MHT in the intracellular MHT group were significantly higher than those in the extracellular MHT group 7 days after MHT, suggesting that the temporal change of MNPs within the tumor in the intracellular MHT group was smaller than that in the extracellular MHT group. Our results suggest that intracellular MHT is more cytotoxic than extracellular MHT in spite of a lower temperature rise of tumors, and that MPI is useful for evaluating the difference in the temporal change of MNPs in the tumor between extracellular MHT and intracellular MHT.展开更多
The primary intent of this paper is to investigate the potential of using a slotted circular patch antenna at 2.45 GHz for breast tumor hyperthermia treatment. A cancer treatment model consisting of a microstrip patch...The primary intent of this paper is to investigate the potential of using a slotted circular patch antenna at 2.45 GHz for breast tumor hyperthermia treatment. A cancer treatment model consisting of a microstrip patch antenna and breast phantom comprising tumor is designed and simulated in CST Studio Suite 2018. The radiation properties of the proposed antenna attain 3 dB beam width of 74.1°and 70.5°for the E-Plane and the H-plane, respectively. The breast phantom is exposed to the designed antenna radiation for 10 minutes, leading to raise the breast phantom temperature by 8.5°C and 11.4°C once the antenna pumped power is 1.5 and 2 watt, respectively. By considering 10 minutes as an exposure time, the breast temperature as a function of the applied antenna power is studied and compared with previous published results.展开更多
Magnetite (Fe3O4) nanoparticles with different magnetic properties were prepared by coprecipitation of Fe3+ and Fe2+ with aqueous NaOH solution. The inductive heat properties of Fe3O4 nanoparticles in an alternating c...Magnetite (Fe3O4) nanoparticles with different magnetic properties were prepared by coprecipitation of Fe3+ and Fe2+ with aqueous NaOH solution. The inductive heat properties of Fe3O4 nanoparticles in an alternating current (AC) magnetic field were investigated for local hyperthermia. The maximum saturation magnetization Ms of Fe3O4 nanoparticles is 65.53 emu·g-1 under the optimum conditions of Fe3+: Fe2+ molar ratio at 1.8:1. The Ms of Fe3O4 nanoparticles decreased as the Fe3+/Fe2+ molar ratio increased. But the coercivity Hc increases with the increasing of Fe3+/Fe2+ molar ratio. Exposed in the AC magnetic field for 29 min, the temperatures of physiological saline suspension containing Fe3O4 nanoparticles were 42-97.5 ℃. The inductive heat property of Fe3O4 nanoparticles in AC magnetic field decreases as Hc increases, but increases with the increasing of Ms. The Fe3O4 nanoparticles would be useful as good thermoseeds for localized hyperthermia treatment of cancers.展开更多
CEM43 thermal dose is a very common concept in thermal oncology.Thermal dose is the maximum amount of energy that can be transmitted during hyperthermia therapy conducted on temperature-sensitive tissue.Thermal dose i...CEM43 thermal dose is a very common concept in thermal oncology.Thermal dose is the maximum amount of energy that can be transmitted during hyperthermia therapy conducted on temperature-sensitive tissue.Thermal dose is also the maximum value of local energy accumulation in human bodies,which can lead to tissue injury and pain.Thermal dose can also decrease the finishing temperature and reduce the energy to the tolerable range.There are two functions of the individualized hyperthermia treatment plan:it determines the setting and location that can realize the best tumor hyperthermia therapy;at the same time,it can decrease the effect of hyperthermia therapy on healthy tissues.There are four steps in the treatment plan of hyperthermia therapy for tumors:the first step is to establish a three dimensional human body model and its corresponding an atomical structure that can be used in numerical algorithm via medical imaging resources;the second step is to determine the volume of the electromagnetic energy accumulation.Based on the peculiarity of frequency and materials,even full-wave electromagnetic wave or quasi-static technique can be used to determine the tissue distribution.Evaluation of the therapy can be conducted based on thermal dose and the corresponding tissue damage model;the third step is to use Arrhenius model to provide direct evaluation of tissues in the thermal ablation zone,solidification zone,as well as the necrotic area;the last step is the optimization of the treatment plan.展开更多
Metaphase-arrest agents and hyperthermia are both known to be capable of inducing apoptosis, and they have been used, separately, in cancer treatments. Here, we have examined whether the two treatments together may ha...Metaphase-arrest agents and hyperthermia are both known to be capable of inducing apoptosis, and they have been used, separately, in cancer treatments. Here, we have examined whether the two treatments together may have a synergistic effect. We find that when H-HeLa cells are arrested in metaphase with spindle poisons (nocodazole or paclitaxel) and then subjected to mild heat treatment (41.5℃), they exhibit morphological changes typical of apoptosis within three hours. Moreover, those changes are blocked by the pan-caspase inhibitor zVAD-fmk, indicating apoptosis, and activated Procaspase 3 is detected by immunoblotting and by staining with the fluoresce-in-labelled caspase inhibitor FAM-VAD-fmk. Interphase cells treated in the same way do not under-go apoptosis, even with spindle poisons present. Induction of apoptosis is more rapid when the cells have been arrested longer in metaphase, suggesting that accumulation or depletion of some cellular component(s) during metaphase-arrest may make them more susceptible to hyperthermia. Further work is in progress to test whether other cell lines exhibit the same behavior and to learn more about the mechanism. The phenomenon is of interest because it may provide clues to how hyperthermia induces cell death and may yield novel therapeutic approaches to block or stimulate apoptosis.展开更多
文摘Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method called magnetic particle imaging (MPI) has been introduced. MPI allows imaging of the spatial distribution of MNPs. The purpose of this study was to investigate the feasibility of visualizing and quantifying the intratumoral distribution and temporal change of MNPs and predicting the therapeutic effect of MHT using MPI. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, mice were divided into untreated (n = 10) and treated groups (n = 27). The tumors in the treated group were directly injected with MNPs (Resovist?) with iron concentrations of 500 mM (A, n = 9), 400 mM (B, n = 8), and 250 mM (C, n = 10), respectively, and MHT was performed using an AMF with a frequency of 600 kHz and a peak amplitude of 3.5 kA/m. The mice in the treated group were scanned using our MPI scanner immediately before, immediately after, 7 days, and 14 days after MHT. We drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels by taking the threshold value for extracting the contour as 40% of the maximum MPI value (pixel value) within the ROI. These parameters in the untreated group were taken as zero. We also measured the relative tumor volume growth (RTVG) defined by (V-V0)/V0, where V0 and V are the tumor volumes immediately before and after MHT, respectively. Results: The average, maximum, and total MPI values decreased up to 7 days after MHT and remained almost constant thereafter in all groups, whereas the number of pixels tended to increase with time. The RTVG values in Groups A and B were significantly lower than those in the control group 3 days or more and 5 days or more after MHT, respectively. The above four parameters were significantly inversely correlated with the RTVG values 5, 7, and 14 days after MHT. Conclusion: MPI can visualize and quantify the intratumoral distribution and temporal change of MNPs before and after MHT. Our results suggest that MPI will be useful for predicting the therapeutic effect of MHT and for the treatment planning of MHT.
文摘Physicians often observe patients’ complexion (their natural skin color) as an indicator of health. The complexion may depend on the internal environment, however, very few researchers studied its evidence. We previously reported various benefits of a mild hyperthermia treatment on human health using the nano-mist sauna (NMS), including acceleration of gas exchange (O2 and CO2) in the venous blood, enhancement of immunity, and the modulation of autonomic nervous system. However, the effects of NMS on skin appearance are unknown. There is a historical and widespread belief that mild hyperthermic treatments such as hot springs are good for improving skin appearance. However, the effect of NMS on the skin appearance has not been examined. In the present study, we examined the color of venous blood using the CIELAB (a color space specified by the French Commission internationale de l’éclairage) method, and then compared the color changes before and after NMS stimulation. Next, we examined correlations of blood gas parameters with color elements of the venous blood, which are highly dependent on oxygen. Our results suggest that the colors and appearance of the face depend on the internal environment, because there are numerous vessels under the skin. Thus, the color of the venous blood may provide medical evidence of changes in complexion. This new method may be useful for assessment of medical complexion by physicians, for use in determining internal health based on skin color information.
文摘Cancer patients with bone metastases in their extremities may require surgical intervention to prevent deterioration in their quality of life due to a pathological fracture or severe bone pain. However, curative surgical interventions sometimes have severe complications due to the status of the original cancers. To avoid the decreased quality of life caused by bone metastasis, minimally invasive surgery that avoids additional surgical morbidity is required. We have established two therapeutic treatments for bone metastasis, a photodynamic acridine orange treatment (AOT) and an electronic magnetic hyperthermia treatment (EMHT). The present study investigated the clinical outcomes of combination therapy with EMHT and AOT for patients with bone metastases in their extremities. Methods: The study included 6 patients with 7 bone cancer metastasis locations. For bone metastases, all patients received intraregional tumor excision supported by AOT, in which photodynamic and radiodynamic therapy kills tumor cells during surgery with minimal damage to normal tissues. After the curettage, bone reconstruction was performed by using magnetic materials with calcium phosphate cement. EMHT was repeatedly performed after surgery. In EMHT, tumor cells are killed with an electric magnetic field generator, and bony union is promoted by electronic stimulation. Results: The mean duration of follow-up was 14 months. During the follow-up period, only one patient experienced a local recurrence, and this recurrence occurred 14 months after surgery. Bony union occurred in 4 of 5 cases (80%), and the pain score was significantly reduced after surgery. Conclusions: In the present study, AOT reduced the invasiveness of surgery. EMHT reduced the tumor growth without major complications and promoted bone formation after surgery. Our clinical results confirmed that EMHT and AOT combination therapy for bone metastasis can preserve limb function without local recurrence or bone absorption.
文摘The purpose of this study was to evaluate the effectiveness of intracellular magnetic hyperthermia treatment (MHT) in comparison with that of extracellular MHT using magnetic particle imaging (MPI). Colon-26 cells were implanted subcutaneously into the backs of 8-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, the mice were divided into control (n = 10), extracellular MHT (n = 8), and intracellular MHT groups (n = 7). In the control group, MHT was not performed. In the extracellular MHT and intracellular MHT groups, the tumors were injected directly with magnetic nanoparticles (MNPs) (400 mM Resovist®) and were heated for 20 min using an alternating magnetic field. During MHT, the temperatures of the tumor and rectum were measured using optical fiber thermometers. In the extracellular MHT group, MHT was performed 15 min after the injection of MNPs, whereas MHT was performed one day after the injection of MNPs in the intracellular MHT group. In both groups, MPI images were obtained using our MPI scanner immediately before, immediately after, and 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, maximum, and total MPI values and the number of pixels within the ROI. Transmission electron microscopic (TEM) images were also obtained from resected tumors. In all groups, tumor volume was measured every day and the relative tumor volume growth (RTVG) was calculated. The TEM images showed that almost all the MNPs were aggregated in the extracellular space in the extracellular MHT group, whereas they were contained within the intracellular space in the intracellular MHT group. Although the temperature of the tumor in the intracellular MHT group was significantly lower than that in the extracellular MHT group, the RTVG value in the intracellular MHT group was significantly lower than that in the control group 2 days or more after MHT and that in the extracellular MHT group 3, 4, and 5 days after MHT. The average MPI value normalized by that immediately before MHT in the intracellular MHT group was significantly higher than that in the extracellular MHT group immediately and 7 days after MHT. The maximum and total MPI values normalized by those immediately before MHT in the intracellular MHT group were significantly higher than those in the extracellular MHT group 7 days after MHT, suggesting that the temporal change of MNPs within the tumor in the intracellular MHT group was smaller than that in the extracellular MHT group. Our results suggest that intracellular MHT is more cytotoxic than extracellular MHT in spite of a lower temperature rise of tumors, and that MPI is useful for evaluating the difference in the temporal change of MNPs in the tumor between extracellular MHT and intracellular MHT.
文摘The primary intent of this paper is to investigate the potential of using a slotted circular patch antenna at 2.45 GHz for breast tumor hyperthermia treatment. A cancer treatment model consisting of a microstrip patch antenna and breast phantom comprising tumor is designed and simulated in CST Studio Suite 2018. The radiation properties of the proposed antenna attain 3 dB beam width of 74.1°and 70.5°for the E-Plane and the H-plane, respectively. The breast phantom is exposed to the designed antenna radiation for 10 minutes, leading to raise the breast phantom temperature by 8.5°C and 11.4°C once the antenna pumped power is 1.5 and 2 watt, respectively. By considering 10 minutes as an exposure time, the breast temperature as a function of the applied antenna power is studied and compared with previous published results.
文摘Magnetite (Fe3O4) nanoparticles with different magnetic properties were prepared by coprecipitation of Fe3+ and Fe2+ with aqueous NaOH solution. The inductive heat properties of Fe3O4 nanoparticles in an alternating current (AC) magnetic field were investigated for local hyperthermia. The maximum saturation magnetization Ms of Fe3O4 nanoparticles is 65.53 emu·g-1 under the optimum conditions of Fe3+: Fe2+ molar ratio at 1.8:1. The Ms of Fe3O4 nanoparticles decreased as the Fe3+/Fe2+ molar ratio increased. But the coercivity Hc increases with the increasing of Fe3+/Fe2+ molar ratio. Exposed in the AC magnetic field for 29 min, the temperatures of physiological saline suspension containing Fe3O4 nanoparticles were 42-97.5 ℃. The inductive heat property of Fe3O4 nanoparticles in AC magnetic field decreases as Hc increases, but increases with the increasing of Ms. The Fe3O4 nanoparticles would be useful as good thermoseeds for localized hyperthermia treatment of cancers.
文摘CEM43 thermal dose is a very common concept in thermal oncology.Thermal dose is the maximum amount of energy that can be transmitted during hyperthermia therapy conducted on temperature-sensitive tissue.Thermal dose is also the maximum value of local energy accumulation in human bodies,which can lead to tissue injury and pain.Thermal dose can also decrease the finishing temperature and reduce the energy to the tolerable range.There are two functions of the individualized hyperthermia treatment plan:it determines the setting and location that can realize the best tumor hyperthermia therapy;at the same time,it can decrease the effect of hyperthermia therapy on healthy tissues.There are four steps in the treatment plan of hyperthermia therapy for tumors:the first step is to establish a three dimensional human body model and its corresponding an atomical structure that can be used in numerical algorithm via medical imaging resources;the second step is to determine the volume of the electromagnetic energy accumulation.Based on the peculiarity of frequency and materials,even full-wave electromagnetic wave or quasi-static technique can be used to determine the tissue distribution.Evaluation of the therapy can be conducted based on thermal dose and the corresponding tissue damage model;the third step is to use Arrhenius model to provide direct evaluation of tissues in the thermal ablation zone,solidification zone,as well as the necrotic area;the last step is the optimization of the treatment plan.
文摘Metaphase-arrest agents and hyperthermia are both known to be capable of inducing apoptosis, and they have been used, separately, in cancer treatments. Here, we have examined whether the two treatments together may have a synergistic effect. We find that when H-HeLa cells are arrested in metaphase with spindle poisons (nocodazole or paclitaxel) and then subjected to mild heat treatment (41.5℃), they exhibit morphological changes typical of apoptosis within three hours. Moreover, those changes are blocked by the pan-caspase inhibitor zVAD-fmk, indicating apoptosis, and activated Procaspase 3 is detected by immunoblotting and by staining with the fluoresce-in-labelled caspase inhibitor FAM-VAD-fmk. Interphase cells treated in the same way do not under-go apoptosis, even with spindle poisons present. Induction of apoptosis is more rapid when the cells have been arrested longer in metaphase, suggesting that accumulation or depletion of some cellular component(s) during metaphase-arrest may make them more susceptible to hyperthermia. Further work is in progress to test whether other cell lines exhibit the same behavior and to learn more about the mechanism. The phenomenon is of interest because it may provide clues to how hyperthermia induces cell death and may yield novel therapeutic approaches to block or stimulate apoptosis.
