(3.235.139.152) 您好!臺灣時間:2021/05/11 12:23
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:顏喬林
研究生(外文):Chiao-Lin Yen
論文名稱:奈米抗癌藥物搭配薑黃素和熱治療對腫瘤療效之探討
論文名稱(外文):Investigation of the Therapeutic Efficacy of Antitumor Nanodrug Combined with Curcumin and Hyperthermia
指導教授:林文澧林文澧引用關係
口試委員:謝銘鈞張富雄
口試日期:2013-07-21
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:2013
畢業學年度:101
語文別:中文
論文頁數:35
中文關鍵詞:薑黃素熱治療奈米抗癌藥物癌症治療
外文關鍵詞:nanodrughyperthermiacurcumincancer treatment
相關次數:
  • 被引用被引用:0
  • 點閱點閱:211
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
薑黃素(curcumin)具有優異的抗氧化、抗發炎等功效,而根據文獻記載,其也有抑制腫瘤生長與轉移的潛力。本研究使用小鼠耳朵腫瘤模式探討奈米抗癌藥物pegylated liposomal doxorubicin (PLD)結合薑黃素和熱治療三者對於腫瘤治療是否有加成的抗癌效果。
本研究使用小鼠耳朵腫瘤模式(Mouse Ear Tumor Model),每隻Balb/c雄鼠左右耳皆植有結腸直腸腺癌CT-26細胞,並於腫瘤長至約50 mm3 開始治療(約接種後10至12天)。實驗共分10個實驗組:控制組、Sham組、Heat組、Curcumin組、PLD組、PLD+Heat+Cur組、PLD+Cur組、PLD+Heat組、Heat+Cur組和Heat+DMSO組。其中奈米抗癌藥物一律經由尾靜脈注射,每週施打一次,劑量為每公斤6毫克,總共治療三次;薑黃素則直接注射於腫瘤組織,劑量為每公斤30毫克,熱治療則是將腫瘤浸泡於43.5℃的溫水浴15分鐘;薑黃素和熱治療則分為不給予或每週給予兩次,治療一共六次。
從實驗結果觀察到抑制腫瘤生長效果最好的三組分別是:PLD+Heat+Cur組、PLD+Heat組和PLD組,三組治療後最終腫瘤體積皆低於治療起始之腫瘤體積。此外,我們也發現當PLD組和PLD+Cur組這兩組加上熱治療後,會比原先沒有熱治療有更好的治療效果,但PLD組和PLD+Cur組相比並無顯著差異存在。另一方面,Heat+Cur組的腫瘤生長也較Heat組腫瘤緩慢,可見熱治療搭配薑黃素比只單獨使用熱治療有更好的腫瘤抑制效果。本研究證明了PLD搭配薑黃素和熱治療的療效優於單獨使用PLD的療效,且在治療中加入熱治療能提高腫瘤對抗癌藥物的敏感度。而在熱治療搭配薑黃素的療程中可以看見薑黃素的輔助效果,但PLD搭配薑黃素卻和單獨給予PLD兩組間卻無顯著差異,應是因為奈米抗癌藥物劑量過高,而無法彰顯出薑黃素的抗癌效果,未來應降低PLD的劑量,以探討其是否能加強PLD的療效。


Curcumin, a natural derivative from Curcumin longa, known for its outstanding antioxidant and anti-inflammatory capabilities, has recently drawn the attention of cancer researchers, showing its ability to inhibit the growth and metastasis of tumors. In the present study, we investigated whether a combination of anticancer nanodrug pegylated liposomal doxorubicin (PLD), curcumin and hyperthermia would have a synergistic antitumor effect in mouse ear tumor model.
In this study, each male Balb/c mouse received implantation of colorectal adenocarcinoma CT-26 cells on both ears. Treatments started whenever tumors grew up to about 50 mm3 (10 to 12 days after tumor cell inoculation). Experiments comprised ten groups:Control, Sham, Hyperthermia only, Curcumin only, PLD only, PLD with curcumin and hyperthermia, PLD with curcumin, PLD with hyperthermia, Hyperthermia with curcumin and Hyperthermia with DMSO. PLD was injected once every week through the tail vein with a dosage of 6 mg/kg, whereas curcumin was administered intratumorally twice a week at the dosage of 30 mg/kg. Semiweekly, tumor tissue was heated to 43.5°C in a water bath for 15 minutes. The above mentioned therapies took three weeks long.
The experiment results showed that PLD+HT+Cur, PLD, PLD+HT were the three groups which demonstrated the best treatment efficacy. Furthermore, PLD or PLD+Cur combined with hyperthermia had better curative effect than without hyperthermia. The present study proved that PLD combined with curcumin and hyperthermia was more effective than PLD alone, and that hyperthermia is able to increase the sensitivity of tumor cells to anticancer drugs. Moreover, curcumin exhibited a great adjuvant effect when combined with hyperthermia to suppress the growth of tumor. However, this wasn''t observed in the PLD+Cur group, which might be the result of the overdose of PLD. Hence, in the future, the dosage of PLD should be lowered, in order to investigate the antitumor efficacy of curcumin.


口試委員會審定書 i
致謝 ii
中文摘要 iv
Abstract v
目次 vii
圖目錄 ix
表目錄 xi
第一章 緒論 1
1.1 腫瘤生成 1
1.2 血管新生 3
1.3 癌症治療 3
1.4 奈米抗癌藥物 4
1.5 薑黃素 5
1.6 熱治療 6
1.7 研究動機與目的 7
第二章 材料與方法 9
2.1 實驗動物 9
2.2 腫瘤細胞株 9
2.3 小鼠耳朵模式 9
2.4 奈米抗癌藥物 10
2.5 薑黃素 10
2.6 熱治療 11
2.7 數值統計與分析方法 11
2.8 實驗設計與流程 12
第三章 結果與討論 15
3.1 控制組和Sham組之比較 15
3.2 Cur組和Heat組之比較 17
3.3 PLD+Cur組和PLD+Heat組之比較 19
3.4 PLD組和PLD+Heat+Cur組之比較 21
3.5 Heat+DMSO組和Heat+Cur組之比較 23
3.6 PLD搭配薑黃素對腫瘤之治療 25
3.7 熱治療搭配薑黃素對腫瘤之治療 26
3.8 PLD搭配薑黃素結合熱治療對腫瘤之治療 28
3.9 各組小鼠體重變化情形 29
第四章 結論與未來展望 31
文獻資料 33


1. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011;144(5): 646-74.
2. Collado M, Serrano M. Senescence in tumours: Evidence from mice and humans. Nature Reviews Cancer 2010;10(1): 51-57.
3. Burkhart DL, Sage J. Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nature Reviews Cancer 2008;8(9): 671-82.
4. Berdasco M, Esteller M. Aberrant epigenetic landscape in cancer: How cellular identitygoes awry. Developmental Cell 2010;19(5): 698-711.
5. Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 2007;26(9): 1324-37.
6. Cong Y, Shay JW. Actions of human telomerase beyond telomeres. Cell Research 2008;18(7): 725-32.
7. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86(3): 353-64.
8. Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics Adriamycin and daunorubicin. Biochemical Pharmacology 1999;57(7): 727-41.
9. Mizutani H, Tada-Oikawa S, Hiraku Y, Kojima M, Kawanishi S. Mechanism of apoptosis induced by doxorubicin through the generation of hydrogen peroxide. Life Sciences 2005;76(13): 1439-53.
10. Chou HH, Wang KL, Chen CA, Wei LH, Lai CH, Hsieh CY, Yang YC, Twu NF, Chang TC, Yen MS. Pegylated liposomal doxorubicin (Lipo-Dox (R)) for platinum-resistant or refractory epithelial ovarian carcinoma: A Taiwanese gynecologic oncology group study with long-term follow-up. Gynecologic Oncology 2006;101(3): 423-28.
11. Koning GA, Eggermont AM, Lindner LH, ten Hagen TL. Hyperthermia and thermosensitive liposomes for improved delivery of chemotherapeutic drugs to solid tumors. Pharmaceutical Research 2010;27(8): 1750.
12. Chinthalapally VR, Abraham R, Barbara S, Bandaru SR. Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Research 1995;55(2): 259.
13. Sharma RA, Gescher AJ, Steward WP. Curcumin: The story so far. European Journal of Cancer 2005;41(13): 1955-68.
14. Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Research 2003;23(1A): 363-98.
15. Sharma RA. Phase I clinical trial of oral curcumin biomarkers of systemic activity and compliance. Clinical Cancer Research 2004;10(20): 6847.
16. Suneet S, Hani Z, Anika H, Bjorn B, Joseph AW, Suresh VA. Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharmaceutical Research 2009;26(2): 480.
17. Zuo L, Christofi FL, Wright VP, Liu CY, Merola AJ, Berliner LJ, Clanton TL.. Intra-and extracellular measurement of reactive oxygen species produced during heat stress in diaphragm muscle. American Journal of Physiology Cell Physiology 2000;279(4): C1058.
18. Fiorentini G, Szasz A. Hyperthermia today: Electric energy, a new opportunity in cancer treatment. Journal of Cancer Research and Therapeutics 2006;2(2): 41-46.
19. Grull H, Langereis S. Hyperthermia-triggered drug delivery from temperature-sensitive liposomes using MRI-guided high intensity focused ultrasound. Journal of Controlled Release 2012;161(2): 317-27.
20. Tonnesen HH, Masson M, Loftsson T. Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility, chemical and photochemical stability. International Journal of Pharmaceutics 2002;244(1-2): 127-35.
21. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: Problems and promises. Molecular Pharmacology 2007;4(6): 807-18.
22. Koning GA, Eggermont AM, Lindner LH, ten Hagen TL. Hyperthermia and thermosensitive liposomes for improved delivery of chemotherapeutic drugs to solid tumors. Pharmaceutical Research 2010;27(8): 1750.

QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
系統版面圖檔 系統版面圖檔