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研究生:游書寧
研究生(外文):Shu-ning Yu
論文名稱:超音波熱效應與機械效應對小鼠癌腫瘤生長之探討
論文名稱(外文):Investigation of Ultrasound Thermal and Mechanical Effects on Growth Response of Mouse Tumors
指導教授:林文澧林文澧引用關係
指導教授(外文):Win-Li Lin
口試委員:謝銘鈞張富雄陳景欣
口試委員(外文):Ming-Jium ShiehFu-Hsiung ChangGin-Shin Chen
口試日期:2015-07-15
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:醫學工程學研究所
學門:工程學門
學類:綜合工程學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:44
中文關鍵詞:超音波熱效應超音波機械效應熱治療癌腫瘤治療
外文關鍵詞:Ultrasound thermal effectsUltrasound mechanical effectsHyperthermiaTumor treatment
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背景: 超音波熱效應對於腫瘤生長的影響已被廣泛的研究,依上升溫度可分為熱治療 (41-45℃) 與熱燒灼手術 (60-100℃),而除了熱效應外,超音波穿過組織亦產生機械效應,機械效應包含空蝕效應、微流,以及輻射力等作用。
目的: 本研究探討超音波熱效應與機械效應對小鼠癌腫瘤生長的影響,以進一步了解機械效應能否有效提升抑制腫瘤生長的機制。

材料與方法: 本實驗使用超音波物理治療機,設定頻率:1MHz、3 MHz;Duty cycle:100%(CW)、50%(PW),熱劑量(CEM43): 4分鐘及30分鐘。實驗組別區分為高熱劑量組與低熱劑量組,分別使用連續式與脈衝式超音波在提供相同熱劑量下,觀察腫瘤成長的影響。CT-26 小鼠結腸腫瘤細胞株 (5*105 cells) 植入小鼠大腿皮下,待腫瘤成長至20mm3後進行治療,每天治療一次,每次10分鐘,共治療14天。利用腫瘤生長曲線與H&E染色切片結果評估超音波熱效應與機械效應對於小鼠癌腫瘤生長的影響。

結果: 實驗結果顯示在低熱劑量下,連續式與脈衝式超音波組在腫瘤大小上,均與控制組無顯著差異,在切片結果顯示控制組的腫瘤細胞較緻密,沒有明顯的淋巴球浸潤與發炎現象,連續式與脈衝式超音波組均可觀察到淋巴球浸潤與發炎現象,腫瘤組織也比較破碎。在高熱劑量下,連續式與脈衝式超音波組在腫瘤的大小,均與控制組有顯著性的差異,連續式與脈衝式超音波組兩者相比,腫瘤體積在治療後第十四天,出現顯著差異,組織切片顯示兩者均可觀察到明顯的淋巴球浸潤與發炎現象,而脈衝式超音波腫瘤細胞排列更為鬆散。
結論: 在低熱劑量下,連續式或脈衝式超音波皆對腫瘤生長無明顯的抑制效果;在高熱劑量的條件下,脈衝式超音波則比連續式超音波有更顯著的腫瘤抑制效果。在腫瘤組織切片上,可觀察到高低熱劑量組別皆有淋巴球浸潤的現象,在高熱劑量的組別其細胞排列更為鬆散。

Background: Ultrasound thermal effect on tumor growth has been extensively studied. It can be divided into hyperthermia (41-45℃) and ablation surgery (60-100℃). Ultrasound passing through tissues also produces mechanical effects, including cavitation, microstreaming, radiation forces, etc.
Purpose: In this study, we investigated the thermal and mechanical effects of ultrasound on tumor growth responses by using continuous wave (CW) and pulsed wave (PW) ultrasound under the same thermal dose.
Materials and methods: In this study, a physiotherapy ultrasound system was used with frequency: 1 MHz, 3 MHz; Duty cycle: 100% (CW), 50%(PW), and thermal dose (TD) CEM43: 4 min, 30 min. Experimental groups were divided into Sham control, Low TDCW, Low TDPW, High TDCW, and High TDPW. Mouse colon cancer cells (CT26, 5*105) were subcutaneously implanted into the right leg of each mouse. The first treatment was conducted when the tumors grew up to 20 mm3, with an ultrasound sonication was 10 min, and the mice were treated every day for 14 days. Tumors were measured every day and H&E staining was used to study the effects of ultrasound on tumor tissues.
Result: In the low TD groups, both CW and PW ultrasound showed no significant difference as compared with the sham control group in tumor growth response. Lymphocytic infiltration and inflammation were observed on the H&E stains for both LTDPW and LTDCW groups, and evidence of tissue rupture. In the high TD groups, a significant difference of tumor growth response could be observed for both CW and PW ultrasound as compared with the sham control group. Comparing the results of HTDCW and HTDPW groups, a significant difference of tumor sizes could be observed on Day 14. H&E stains from both HTDCW and HTDPW groups revealed lymphocytic infiltration and inflammation. Additionally, tumor structure and cells appeared looser for the HTDPW group.
Conclusion: A low TD could not effectively inhibit the tumor growth, but a high TD could. PW ultrasound could further inhibit the tumor growth significantly, maybe due to mechanical effect. H&E stains showed the lymphocytic infiltration, inflammation and tissue disruption, indicating the thermal/mechanical effects of ultrasound on tumor tissues.


致謝 i
摘要 ii
Abstract v
第一章 緒論 1
1.1腫瘤 1
1.2腫瘤治療 3
1.3細胞週期 5
1.4超音波 9
1.5 超音波生物效應 9
1.6研究目的與動機 13
第二章 材料與方法 14
2.1 腫瘤細胞株 14
2.2 實驗動物 14
2.3 小鼠腫瘤模式 14
2.4 超音波設備 15
2.5 超音波平面探頭聲場分布測試 17
2.6 溫度量測系統與溫度測試 18
2.7 動物實驗設計與流程 20
2.8 組織切片染色及判讀 22
2.8 數值統計及分析 24
第三章 結果與討論 25
3.1 超音波平面探頭聲場壓力分佈量測結果 25
3.2 熱效應溫度量測分析與討論: 28
3.2 治療方式對癌腫瘤生長及體重變化討論 31
3.2.1 低熱劑量組別與Sham control之比較 31
3.2.2 高熱劑量組別與Sham control之比較 34
3.3 討論 39
第四章 未來展望 41
第五章 參考文獻 42



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