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系統識別號 U0026-2607201115094600
論文名稱(中文) 冷凍手術抵抗性癌細胞之機轉研究
論文名稱(英文) The study of mechanisms contributing to cryosurgery- resistant cancer cell
校院名稱 成功大學
系所名稱(中) 生物化學暨分子生物學研究所
系所名稱(英) of Biochemistry and Molecular Biology
學年度 99
學期 2
出版年 100
研究生(中文) 陳婷婷
研究生(英文) Ting-Ting Chen
學號 s1697103
學位類別 碩士
語文別 英文
論文頁數 33頁
口試委員 指導教授-王德華
口試委員-賴明德
口試委員-呂增宏
中文關鍵字 冷凍手術治療  侵略性  抗性  Focal adhesion kinase  黑色素癌 
英文關鍵字 cryosurgery  invasion  resistant  focal adhesion kinase  melanoma 
學科別分類
中文摘要 冷凍治療以普遍用來治療早期黑色素腫瘤、前列腺癌、腎癌與子宮頸癌等不同的癌症,但關於從冷凍治療存活下來的癌細胞之性狀特性了解甚少,利用反覆冷凍解凍之方式產生具有冷凍抗性的小鼠黑色素腫瘤細胞。這些具有冷凍抗性的細胞株的性狀與其原始細胞株在生物體外及生物體內相互比較,從冷凍治療存活下來的細胞之生長速度較快,且在細胞黏著性、爬行能力以及入侵能力的性狀上,具更惡性之表現;然而,這些具有冷凍抗性的細胞仍具有對dacarbazine之敏感度。經由尾靜脈注射抗凍細胞轉移到肺部的腫瘤較少,在生物體內之性狀差異值得更進一步的研究,在這些細胞之磷酸化的focal adhesion kinase、paxillin、Src 與ERK之表達皆有上升的現象,關於具有冷凍抗性的癌細胞之機轉部分與FAK/Src 之訊息傳導有關。
英文摘要 Cryosurgery is widely used to treat different cancers including early malignant melanoma, prostate cancer, renal tumor and cervical intraepithelial neoplasm. Little is known about the phenotype of cancer cells that survived after cryosurgery. The cryosurgery-resistant B16F10 murine melanoma cells were established by exposing cells to freeze-thaw cycles in vitro repeatedly. The phenotype of resistant cells was compared with their original cells in vitro and in vivo. Cells survived cryosurgery grew faster and showed more aggressive phenotype on cell adhesion, migration and invasion. However, the cryo-resistant cells remain sensitive to dacarbazine. Less lung metastases were found after intravenous injection of resistant cells. The difference in in vivo phenotype merits further clarification. The expressions of phosphorylated forms of focal adhesion kinase, paxillin, Src and ERK were upregulated in these cells. The mechanism was at least partly related to the FAK/Src signaling pathway.
論文目次 Abstract I
Acknowledgement III
Abbreviations V
Introduction 1
1. Materials and Methods 4
1.1 Cells 4
1.2 Generation of cryosurgery resistant cells 4
1.3 Cell proliferation 5
1.4 Cell adhesion 5
1.5 Cell migration 5
1.6 Cell invasion 6
1.7 Colony formation in soft agar 7
1.8 Cytotoxicity of chemotherapeutic agent 7
1.9 Western blotting 7
1.10 Lung metastasis 8
1.11 Statistical analysis 8
2. Results 8
2.1 Cells exposed to repeated freeze-thaw are highly proliferated cells 8
2.2 Cells after cryosurgery are more adhesive 9
2.3 Cryosurgery enhances cell motility 9
2.4 Cryo-resistant melanoma cells are more invasive 9
2.5 More colonies formed in R9 melanoma cell line 10
2.6 Cytotoxicity of chemotherapeutic agent 10
2.7 Less tumor metastasize to lung in cryo-resistant melanoma cells. 10
2.8 Proteins involved in focal adhesion complex are activated with cryosurgery. 10
3. Discussion 12
4. References 15
5. Figure legends 20
6. Figures 23
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