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標題: | 選擇波段紅外光照射子宮頸癌HeLa細胞以增進紫杉醇的抑癌應用 Enhancement of Taxol effectiveness on HeLa cells by Selected broad Bandwidth infrared radiation (IR) |
作者: | Pei-Shen Huang 黃佩慎 |
指導教授: | 許博欽 |
關鍵字: | 子宮頸癌HeLa細胞,人類乳突病毒,光動力治療,可調控波長紅外光,紫杉醇, HeLa cell,Human papilloma virus (HPV),Photodynamic therapy (PDT),Selected broad bandwidth infrared radiation (IR),Paclitaxel (Taxol), |
出版年 : | 2013 |
學位: | 碩士 |
摘要: | 子宮頸癌在台灣仍是高居不下的女性癌症,每年約有1700人診斷為新病例,並有將近600人死於子宮頸癌。近代子宮頸癌症的治療,疾病早期需接受根除性子宮全切除手術,後續會有很多全身性的副作用(排尿、解便困難);疾病晚期無法接受開刀的病患,多是利用化學藥劑加上輻射治療,在治療子宮頸癌上已有相當程度的功效,但是全身性的副作用也不容小覷。
目前在高致癌型人類乳突病毒持續性感染和癌前病變階段,也無較好的預防或治療。臨床上僅能定期以抹片、切片等方式追蹤其變化,必要時需要切除以避免進一步癌症的發生。如果紅外光照射後,可以讓致癌型人類乳突病毒持續性感染消失,延緩癌變的進展,或進一步導致子宮頸癌HeLa細胞凋亡,照射紅外光就對治療子宮頸上皮病變及子宮頸癌有幫助。 由於子宮頸位於體表且避光的獨特生理位置,非常適合使用光動力治療,配合局部化學或放射線治療。目前光動力治療在台灣仍未被廣泛的接受,主要是因為光敏劑和雷射光源的價格很高的關係。本研究的主要目標,藉由調控適當波段的紅外光IR取代雷射光源,配合適當的藥物(吸收峰在光源範圍內或現行使用的化學藥物)取代光敏劑,來觀察子宮頸癌HeLa細胞生長型態的改變,減低癌細胞增生和侵略性。 本實驗室研發的高功率波導型熱輻射發射器(waveguide Thermal Emitter) ,其三層結構(金/二氧化矽/金),讓位於上下兩層金之間的二氧化矽可產生共振腔膜態,產生紅外光源,做為氣體偵測、生命科學研究,以及生醫工程的應用。 我們應用同樣的紅外光源,加入水冷系統微型化後,置入生長箱設定出穩定的照光環境(5% CO2,37.0±0.5℃)。第一階段的實驗,將人類子宮頸癌HeLa細胞進行單獨照光分析結果。 第二階段的實驗,選用現階段婦產科化學治療中最熱門的藥物-紫杉醇(Paclitaxel,商品名 Taxol),依藥物吸收頻譜,調整紅外光照射的波段,選定藥物最小抑癌濃度,進行反覆的照光實驗,最後進行各種細胞的分析。初步研究成果發現,紅外光可提升紫杉醇的治療效果。本計畫進一步推測了可能的機轉,探究是否紅外光可刺激癌細胞的粒線體膜電位變化,和產生大量活性氧 (reactive oxygen species, ROS),或是增進紫杉醇與子宮頸癌HeLa細胞的結合比率,進而提升紫杉醇Paclitaxel治療效果。 Cervical cancer is the third most common cancer in women, with an estimated 530 000 new cases in 2008. More than 85% of the global burden occurs in developing countries, where it accounts for 13% of all female cancers. High-risk regions are Eastern and Western Africa, Southern Africa, South-Central Asia, South America and Middle Africa. Rates are lowest in Western Asia, Northern America and Australia/New Zealand. Cervical cancer remains the most common cancer in women only in Eastern Africa, South-Central Asia and Melanesia. Overall, the mortality: incidence ratio is 52%, and cervical cancer is responsible for 275 000 deaths in 2008, about 88% of which occur in developing countries: 53 000 in Africa, 31 700 in Latin America and the Caribbean, and 159 800 in Asia. Cervical cancer in Taiwan is still ranking primary in female cancer. About 6,000 people each year were diagnosed with new cases (including carcinoma in situ and invasive carcinoma), and nearly 900 people each year died of cervical cancer. Modern treatment of cervical cancer, the early stage patients accept radical hysterectomy, and there will be lots of systemic side effects such as difficulty in urination and defecation; the late stage patients can’t accept surgery, will receive chemotherapy plus radiation therapy. Chemotherapy combined with radiotherapy has been effective in some degrees of treating cervical cancer; however systemic side effects should not be underestimated. In previous study showed that persistent chronic infection with human papilloma virus (HPV) causes cervical intraepithelial lesions, further progress turned to cervical cancer in few years later. Simple HPV infection or mild cervical intraepithelial lesion treatment, recommended primary care with regular pap smear, colposcopy or biopsy when it is indicated. If the Infrared (IR) light irradiation can postpone the progression of the disease and induced HeLa cells apoptosis, IR may help in the treatment of cervical intraepithelial lesions and cervical cancer. The position of cervix is suitable for the use of photodynamic therapy combined with local chemical or radiation therapy due to its surface condition and the dark environment. Patients in Taiwan still not accept photodynamic therapy widely, because of the costs of the photosensitizer and laser light source. The main objective of this study, laser light is replaced by selected broad bandwidth infrared radiation, and photosensitizer is replaced by Paclitaxel. If the drug effect increased on HeLa cells irradiated by selected broad bandwidth infrared radiation, it changed the growth patterns of HeLa cells, and reduced cancer cell proliferation and progress. In recent years, our group demonstrated tri-layers Au/SiO2/Au waveguide thermal emitter (WTE) as the selected broad bandwidth IR light source. The cavity mode resonance is generated in the SiO2 layer between two Au films. It can be applied in gas sensing, life science research and biomedical engineering. We apply the same miniaturization infrared light source with cooling system, placed in a growth chamber with a stable environment (5% CO2,37.0±0.5℃) in our study.The first phase of the experiment, the human cervical cancer cell line HeLa cells firstly irradiated by selected broad bandwidth 3-5μm IR radiation without drugs. The second phase of the experiment, we choose Paclitaxel to study the effectiveness on HeLa cells with selected broad bandwidth IR radiation.Preliminary reports have found that IR can enhance the therapeutic effect of Paclitaxel. So we will continue to clarify the mechanism if IR may regulate mitochondrial membrane potential and produce a large amount of reactive oxygen (ROS) to enhance the effectiveness of Paclitaxel treatment. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/15690 |
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顯示於系所單位: | 臨床醫學研究所 |
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