• Herbal Formula Science
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• v.27 no.1
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• pp.45-52
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• 2019

Objectives : Hyperthermia is a widely used therapeutic tool for cancer therapy and a well-known inducer of apoptosis. Although the Cinnamomi cortex (CC) is a potent anticancer agent for several human carcinomas, it is less potent in the human U937 cell line. To explore any enhancing effects of CC with hyperthermia induced apoptosis, this study investigated the combined effects and apoptotic mechanisms of hyperthermia and CC in U937 cells. Methods : U937 cells were heat treated at $43^{\circ}C$ for 30 min with or without pre-treatment for 1h with CC and then incubated at $37^{\circ}C$ with 5% $CO_2$. Cell viability was analyzed by MTT assay and Trypan blue assay. Morphological changes reflecting apoptosis were visualized under microscope. Synergy effect of CC combined with hyperthermia were calculated by Compusyn software. The expression of proteins related to apoptosis and signaling pathways was determined by western blotting. Results : Hyperthermia with CC reduced cell viability and induced apoptosis. Combined hyperthermia and CC treatment markedly augmented apoptosis by upregulating proapoptotic proteins and suppressing antiapoptotic proteins, culminating in caspase-3 activation. Furthermore, the combined treatment, decreased the expression of in Bcl-2 family, cyclin D1, VEGF, MMP2 and MMP9 expression. Conclusion : This study provides compelling evidence that hyperthermia, in combination with CC, is a promising therapeutic strategy for enhancement of apoptosis and suggests a promising therapeutic approach for cancer.

• Environmental Mutagens and Carcinogens
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• v.15 no.2
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• pp.88-93
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• 1995

Effects of hyperthermia on the induction of DNA single strand breaks and replication inhibition were studied in bleomycin-treated CHO-K$_1$ cells by alkaline elution and alkaline sucrose gradient sedimentation. Bleomycin-induced DNA single strand breaks of DNA were dose-and time-dependently increased, and these strand breaks of DNA were gradually rejoined as post-incubation time passed. Treatment with hyperthermia alone did not affect the induction of DNA single strand breaks. However, pre-exposure of cells to hyperthermia followed by bleomycin treatment greatly increased the single strand breaks, and also reduced the rejoining processes of bleomycin-induced DNA single strand breaks. Bleomycin selectively inhibited the replicon initiation. The combined treatment with hyperthermia and bleomycin markedly potentiated the nonspecific inhibition of replication.

• Radiation Oncology Journal
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• v.2 no.2
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• pp.167-171
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• 1984

The renewed interest in the use of hyperthermia in cancer therapy is based on radiobiological and clinical evidence indicating that there may be significant thereapeutic advantages with the use of hyperthermia alone or combined with irradiation plus heat. Authors performed the experiment using the chemically induced mammary carcinoma of rats to observe the difference in temperature changes between tumor and normal tissue during heat, and to compare the response of the tumors to radiation alone and to radiation plus hyperthermia. The results were as follows 1. Temperature of tumors was significantly higher than in the normal tissue during heating and the difference was about $1.5^{\circ}C$. 2. $TCD_{50}$ in radiation alone and hyperthermia immediately following radiation was 1,282 rad and 795 rad, respectively and TER value was 1.81.

• Radiation Oncology Journal
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• v.2 no.1
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• pp.21-23
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• 1984

Temperature homogeniety and stationary temperature is the most important thermometric considerations for the clinical use of hyperthermia. A thermal mapping was done in a phantom with thermocouple during hyperthermia which was induced by 1.0MHz,$0.7\~0.8watts/cm^2$ ultrasound and unfocused 2.5cm-diameter transducer. The results were as follows 1. Effective heating range$(42.5^{|circ}C\pm0.5^{\circ}C)$ were obtained 3cm in width and 4cm in depth from surface of phantom and temperature distribution was relatively uniform. 2. There was little heating effect more than 2cm away from transducer axis and more than 5cm in depth. 3. There was hot spots(more than $43^{\circ}C$) in $2.0\pm0.5cm$ depth from transducer along tranducer axis.

• Korean Journal of Veterinary Research
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• v.59 no.2
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• pp.59-67
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• 2019

We investigated whether ${\beta}$-carotene (${\beta}-CA$) or ellagic acid (EA), originating from various fruits and vegetables, has a preventive effect against male infertility induced by exogenous scrotal hyperthermia. ICR adult mice were intraperitoneally treated with 10 mg/kg of ${\beta}-CA$ or EA daily for 13 days consecutively. During this time, mice were subjected to transient scrotal heat stress in a water bath at $43^{\circ}C$ for 20 min on day 7, and their testes and blood were obtained on day 14 for histopathologic and biochemical analyses. Heat stress induced significant testicular weight reduction, germ cell loss and degeneration, as well as abnormal localization of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and manganese superoxide dismutase (MnSOD) in spermatogenic and Leydig cells. Heat stress also altered the levels of oxidative stress (lipid peroxidation, SOD activity, and PHGPx, MnSOD, and $HIF-1{\alpha}$ mRNAs), apoptosis (Bax, Bcl-xL, caspase 3, $NF-{\kappa}B$, and $TGF-{\beta}1$ mRNAs), and androgen biosynthesis (serological testosterone concentration and $3{\beta}$-hydroxysteroid dehydrogenase mRNA) in testes. These changes were all improved significantly by ${\beta}-CA$ treatment, but only slightly improved by EA treatment. These findings indicate that ${\beta}-CA$, through modulations of oxidative stress, apoptosis, and androgen biosynthesis, is a potent preventive agent against testicular injuries induced by scrotal hyperthermia.

• Journal of Pharmaceutical Investigation
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• v.37 no.3
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• pp.131-135
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• 2007

A previous report recently demonstrated that ultrasound-induced hyperthermia (USHT:0.4 watts (W)/$cm^2$ at $41^{\circ}C$) could increase cellular uptake of P-glycoprotein (P-gp) substrates in P-gp expressing cancer cell lines. Since P-gp plays a major role in limiting drug permeability in the multi-drug resistant (MDR) cells, studies were conducted to elucidate the mechanism of USHT on cellular accumulation of P-gp and non-P-gp substrate in MDR cells. To accomplish this aim, we studied the effects of USHT on the accumulation of P-gp substrate, R123 and non-P-gp substrate, antipyrine in MDR cells. We demonstrated that USHT increased permeability of hydrophobic molecules (R123 and $[^{14}C]$-antipyrine). The enhanced permeability is reversible and size-dependent as USHT produces a much larger effect on cellular accumulation of $[^{14}C]$-antipyrine (MW 188) than that of R123 (MW 380.8). These results suggest that USHT could affect MDR cells more sensitive than BBMECs. Also, the present results point to the potential use of USHT to increase cellular uptake of P-gp recognized substrates, mainly anti-cancer agents into cancer cells.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.114-114
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• 2003

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.6
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• pp.345-349
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• 2004

Heat shock ($43^{\circ}C$ for 60 minutes) is sufficient to induce apoptosis in a wide number of cell lines. In this study, we asked whether DNA strand breaks are responsible for this phenomenon. Using the highly sensitive comet assay for DNA damage detection, we were unable to demonstrate DNA breaks immediately after heat shock in Raji human Iymphoid cells. It showed that DNA breaks were not necessary for hyperthermic apoptosis, since its activity is indicative of DNA lesions. Here, we present a suggestion that a protein(s) is the major target for heat shock apoptosis. We firstly found glycerol, which reportedly stabilizes protein structure, showed a protective effect in Raji cells against hyperthermic apoptosis. In addition, quercetin, which modulates transcription of the heat shock protein family members, enhanced apoptotic death induced by hyperthermia. Furthermore, Raji cells are protected by a pre-mild heat treatment prior to the killing dose of heat shock.

• Journal of Biomedical Engineering Research
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• v.30 no.5
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• pp.418-427
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• 2009

As many people are westernizing their life style and food consumption habits, a number of patients who have malignant tumors which grow very rapidly and hazardously destroy the human body are increasing. Ultrasonic hyperthermia is not only one of the tumor treatment methods which employs the non-radioactive ultrasonic waves to increase the temperature at the tumor region up to $40\sim45^{\circ}C$ to destroy and suppress tumor cells but also has been proved by many studies. Due to the rapid development of High Intensity Focused Ultrasound(HIFU), the ultrasound hyperthemia extensively boosts its applications in clinical field. For those reasons, Computed simulation factor should be needed before inspection to patients. To prove efficiency of ultrasonic hyperthermia, precise acoustic field measurement considering tissue characteristics and a heating experiment with tissue mimicking material phantom were conducted for effectiveness of simulation program. Finally, in this study, the computer simulation program verified the anticipated temperature effects induced by ultrasound hyperthermia. In the near future, it is hoped that this simulation program could be utilized to improve the efficiency of ultrasound hyperthermia.

• Korean Journal of Head & Neck Oncology
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• v.6 no.1
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• pp.40-45
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• 1990

Thirty five lesions of 35 patients with locally advanced malignant tumors of head and neck were received thermoradiotherapy with ultrasound and/or 915 MHz microwave. Most of all patients were failed with previous conventional therapeutic trial. Hyperthermia had been done immediately after radiotherapy, twice a week, $43^{\circ}C$ for one hour and radiotherapy had been done 5 fractions per week with a fraction size of 2 Gy up to total 30 to 60 Gy. Conclusions are as follows; 1) Total response rate (CR+PR) of thermoradiotherapy with microwave and ultrasound was 80%. 2) Tumor depth, minimum temperature of tumor center, number of heat fraction and irradiation dose were statistically significant factors affecting response. 3) Hyperthermia with microwave and ultrasound can be used efficiently to control locally advanced malignant tumors in head and neck whether previously received near tolerance dose of radiotherapy or not.