この研究は、外部マイクロ波（EMW）ハイパーサーミアシステム（2.45 GHz）の治療有効性を、インビトロおよびインビボで評価した。3つの異なる非小細胞肺がん細胞および正常な線維芽細胞（対照）を、弱（39 °C）、中（43 °C）、強（47 °C）に設定したプロトタイプEMWシステムで、1日1回、3日間処理した。 4日目に、試験した細胞を回収し、アポトーシスアッセイおよびウエスタンブロット分析で検査した。その結果、中レベル温熱療法群では、がん細胞は有意なアポトーシスを示し、その一方、正常な線維芽細胞に大きな損傷は観察されなかった；ウエスタンブロット分析では、カスパーゼ-3、-9およびPARPの切断が示された；また、細胞周期分析では、サブG0-G1集団の増加が確認された、と報告している。その次に、体内加熱強度を最適化した後、24匹の免疫不全マウスで胸膜転移モデルを作成し、播種性腫瘍増殖に対する全身性EMW温熱療法の抑制効果を評価した。24匹のマウスのうち、8匹は軽度、8匹は中等度の温熱療法を受け、残りの8匹は無治療対照とした。その結果、治療群での胸膜および胸腔周辺に転移した腫瘍は、未治療対照群と比較して、サイズと重量が75 %減少した；中等度の温熱療法群から摘出した腫瘍組織において有意なアポトーシスが確認された、と報告している。
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To study the effects of external microwave hyperthermia on apoptosis and cell viability in three different cancer cell lines and in fibroblasts (as controls) and in a in vivo pleural metastasis animal model.
Mice were divided into three groups (8 mice/group): control group and two exposed group (mild, 39°C and moderate, 43°C). Orthotopic tumors are usually established on the lung or on the inner thoracic membrane 10-14 days after tumor inoculation. Mice were treated either by mild or moderate microwave hyperthermia on days 12, 13, 14, 19, 20, and day 21 after tumor inoculation. Seven days after the last treatment all mice were sacrificed.
| ばく露 | パラメータ |
|---|---|
|
ばく露1:
2.45 GHz
ばく露時間:
three times (3 sec (37° C = control group), 4 sec (39° C) or 5 sec (43° C)) with a 2 sec interval; 3 days/week for 2 weeks
animal study
|
|
|
ばく露2:
2.45 GHz
ばく露時間:
three times (3 sec (37° C = control group), 5 sec (39° C), 7 sec (43° C) or 9 sec (47° C)) with a 2 sec interval; 3 days/week
in vitro study
|
| 周波数 | 2.45 GHz |
|---|---|
| タイプ |
|
| ばく露時間 | three times (3 sec (37° C = control group), 4 sec (39° C) or 5 sec (43° C)) with a 2 sec interval; 3 days/week for 2 weeks |
| Additional information | animal study |
| ばく露の発生源／構造 |
|
|---|---|
| ばく露装置の詳細 | two microwave generators mounted vertically into a console facing each other ; cells or animals placed between the two generators |
| 周波数 | 2.45 GHz |
|---|---|
| タイプ |
|
| ばく露時間 | three times (3 sec (37° C = control group), 5 sec (39° C), 7 sec (43° C) or 9 sec (47° C)) with a 2 sec interval; 3 days/week |
| Additional information | in vitro study |
| ばく露の発生源／構造 |
|
|---|
The data revealed that cancer cells treated with moderate hyperthermia (43°C) showed significant apoptosis; the induction of apoptosis and the accumulation of sub G0 phase-G1 phase cells were dramatically increased in temperature dependent manner in the three cancer cell lines treated with microwave hyperthermia compared to untreated control cells. In contrast, no major effect was observed to normal fibroblast cells.
Western blot analysis indicated that the strong induction of apoptosis in hyperthermia exposed cancer cells is mediated both by the activation of caspase cascade and apoptotic regulation of Bcl-2 family.
The data of the in vivo investigation showed that metastasized tumors around the pleura and chest cavity were 75% reduced in size and weight after hyperthermia treatment compared to the control group. Harvested tumors demonstrated significant apoptosis in the moderate hyperthermia group. No significant adverse effects were observed including abnormal weight loss, skin burn, ulceration, and death.
The external microwave hyperthermia system may be possible alternative tool as a systemic hyperthermia therapy in severely advanced lung cancer patients. Further study is necessary to determine device safeness, efficacy, and synergistic effect to other possible combination therapies.
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