Enhancement of Immunological Activity and drug Uptake to Tumor by Mild-Hyperthermia.

温和高温增强肿瘤的免疫活性和药物摄取。

• 批准号: 16591234
• 负责人: HASEGAWA Takeo
• 金额: $ 2.11万
• 依托单位: Suzuka University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591234/
• 关键词: Mild Hyperthermia; Immunological Activity; Increased of Blood Flow; Drug Uptake; Anti-Tumor Effect; 化学療法; シスプラチン; 血管拡張; 薬剤取込み増加; アポトーシス; NK細胞活性

In general, hyperthermia (HT) therapy is performed at a temperature of 42.5℃ for 1 hour. It is believed that mild HT at 39℃ to 40℃ brings no anti-tumor effects in the in vitro system. But in the present study, we found that there were anti-tumor effects even when at a temperature of 39℃ to 40℃ in vivo due to activation of immunological status. The tumor cells were transplanted on the right thigh of mice. HT was brought by giving a heat to the right thigh in a controlled water bath at 39℃ to 40℃ for 1 hour. After giving the mild HT, NK cells activity and the numbers of white blood cells, lymphocyte cells, granulocyte, and monocyte increased transiently in comparison with those in the pre-heated condition. A delay in SCC-VII tumor growth in C3H mice and a failure in the implantation of tumor were also observed after the mild HT. The chemotherapy combined with mild-HT were increased the anti-tumor effect due to the increase of drug uptake into the tumor tissues. HT were carried out at 41 … More degree for 30 min and combined with cisplatin (7mg/kg, IP) as anti-cancer drug. But combined with mild-HT were 7-times of drug concentration higher than drug alone group in the tumor tissues. When combined with mild-TH and chemotherapy, tumor growth delay were significantly increased combined with heat alone or drug alone treatment. The HT has effect of enhanced the permeability of the cell membrane. These results suggest that HT has effect of increase of blood flow due to the vasodilatation and cell membrane were changed to high permeability of the drug due to the reduced the function of ion channels. Therefore, the chemotherapy may reduced the drugs using mild-HT and it can be reduced the side effects for treatment of tumor on clinically. Mild HT seems to be a useful and effective auxiliary therapy which is not only effective for the treatment of malignant tumors but also for the treatment of diseases related to immunological disturbances such as hepatitis type C, AIDS etc because of no any side effects. And HT has effects of vessel dilatation and increased a blood flow in the heating areas. Less

一般来说，热疗(HT)是在42.5℃的温度下进行1小时。在体外实验中，认为39℃~40℃的轻度羟色胺没有抗肿瘤作用。但在目前的研究中，我们发现在体内，由于免疫状态的激活，即使在39℃到40℃的温度下也有抗肿瘤的作用。将肿瘤细胞移植于小鼠右大腿。通过在39℃至40℃的受控水浴中对右侧大腿加热1小时来进行热疗。给予轻度高温后，与预热状态相比，NK细胞活性和白细胞、淋巴细胞、粒细胞、单核细胞数量有一过性升高。轻度高温后，C3H小鼠SCC-VII肿瘤生长延缓，肿瘤种植失败。化疗联合轻度羟色胺可增加肿瘤组织对药物的摄取，从而增强抗肿瘤作用。在41…时进行高压氧治疗30min，联合顺铂(7 mg/kg，ip)作为抗癌药物。而联合用药组肿瘤组织中的药物浓度比单纯用药组高7倍。联合温和化疗组与单纯热疗组或单用药物组相比，肿瘤生长延迟率明显增加。羟色胺具有提高细胞膜通透性的作用。提示羟色胺具有扩张血管、增加血流量、降低离子通道功能而使细胞膜向高通透性转变的作用。因此，化疗可以减少使用轻度羟色胺的药物，可以减少临床上治疗肿瘤的副作用。轻度高温是一种有效的辅助治疗方法，不仅对恶性肿瘤有效，而且对丙型肝炎、艾滋病等与免疫功能紊乱相关的疾病也有效，且无任何副作用。高压氧具有扩张血管、增加热区血流量的作用。较少

项目成果

Effects of Long Term Oral Administration of Green Tea Cultivated in Defferent Districts in Japan on Body Weight, Blood Lipid and Glucose Levels on db/db Mice.

长期口服日本不同地区种植的绿茶对 db/db 小鼠体重、血脂和血糖水平的影响。

• 发表时间: 2005
• 期刊: Journal of Food Biochemistry. 29
• 作者: Kayoko Maeda;Takeo Hasegawa;Kousuke Murabayashi;Atsushi Fukuyama;Michihiro Ohya.
• 通讯作者: Michihiro Ohya.

The Drug Uptake in the Tumor When the Mild-Hyperthermia Treatment in Combination with the Chemotherapy in vivo.

体内温和热疗联合化疗时肿瘤的药物摄取。

• 发表时间: 2006
• 期刊: JPN, Journal of Hyperthermic Oncology. Vol.22, No.1
• 作者: Hirobumi Ono;Satoshi Ando;Tomoaki Suzuki;Hajime Monzen;Morikazu Amano;Kaoru Terai;Tohru Takahashi;Takeo Hasegawa.
• 通讯作者: Takeo Hasegawa.

Method of Duplicating Film Using the Yeast-derived β-glucan in Mice.

使用酵母来源的β-葡聚糖在小鼠体内复制薄膜的方法。

• 发表时间: 2005
• 期刊: Research Reports of Suzuka University of Medical Science. No.12
• 作者: Atsushi Fukuyama;Satoshi Ando;Kayoko Maeda;Kazushi Ida;Tomokuni Suzuki;Kousuke Murabayashi;Takeo Hasegawa.
• 通讯作者: Takeo Hasegawa.

Comparisons of the Suppressive Effects on Tumor Growth by Different Combinations of Administration of Arsenic Trioxide and Hyperthermia.

三氧化二砷与热疗不同组合对肿瘤生长的抑制效果比较。

• 发表时间: 2005
• 期刊: Japanese Journal of Hyperthermic Oncology. 21・(2)
• 作者: T.Suzuki;H.Monzen;T.Hasegawa et al.
• 通讯作者: T.Hasegawa et al.

Embryonic Death Effects of Hyperthermia Induced by RF(Radiofrequency) Waves.

RF（射频）波引起的高温引起的胚胎死亡效应。

• 发表时间: 2006
• 期刊: Medicine and Biology. Vol.150, No.3
• 作者: Young-Nam Kang;Toshihiro Maenaka;Yuka Itokawa;Takenori Yamashita;Takashi Nakamura;Masami Oshima;Takeo Hasegawa;Ikukatsu Suzuki;Kaori Tano;Torao Ishida;YeunHwa Gu.
• 通讯作者: YeunHwa Gu.