癌症為一種細胞不正常再生並入侵或轉移至其他組織的疾病並且為全球第二大死因，在癌症的化學藥物治療中，常誘發周邊神經產生病變並迫使降低藥物劑量或終止療程而造成病人的死亡。然而目前此病變作用機轉仍未有定論，故本研究以力學之觀點探討此問題。
本研究以紫杉醇施加於PC-12類神經細胞以模擬人體內神經細胞受紫杉醇之影響，引入臨床現行施打計劃下血漿中的紫杉醇濃度，探討兩種施打計畫對活體PC-12細胞黏彈性力學的影響。以原子力顯微鏡對受損之細胞進行應力鬆弛試驗，並分別以類線性黏彈模型與有限元素法估測細胞黏彈之力學性質。另外，應用共軛對焦顯微鏡建立包含細胞本體與細胞核之三維有限元素模型，並以軸對稱模型所得材料參數模擬單顆細胞三維應力鬆弛。類線性黏彈模型分析顯示細胞結構阻尼參數短時注射組之變化大於長時注射組，表示短時注射對細胞之黏滯性影響較大。有限元素分析顯示藥物濃度改變對細胞核之機械性質之影響不明顯，藥物主要影響細胞胞漿，驗證紫杉醇改變細胞內微管分佈從而造成機械性質之改變。切楊氏模數結果發現短時注射組於施打過程中(12hr)有最劇烈之硬度變化並於施打結束後使細胞變軟，長時注射則是先使細胞變軟後於施打結束後趨於正常值。

關鍵字：生物力學、紫杉醇、化療引發周邊神經病變、類線性黏彈理論、共軛聚焦顯微鏡光學切片術、三維影像模型重建、有限元素法

Chemotherapy treatment of cancer by paclitaxel often results in peripheral neuropathy which is a main reason for patients to withdraw from therapy and reduce the survival rate. Most past researches of chemotherapy induced peripheral neuropathy (CIPN) focused on biochemical field. The goal of this thesis is using finite element (FE) method and quasi-linear viscoelasticity (QLV) theory to analyze the indentation of PC-12 cells subjected to in vitro simulations of two clinical paclitaxel doses. Mechanical properties of the cells were measured by curve fitting to both QLV theory and a FE model. Stress-strain relationship was derived from hyperelastic part for comparison purpose. Full 3D cell geometry model was built from confocal microscope immunofluorescences images of the cells. QLV results show that apparent Young’s modulus rises at 12 hours then goes down at 18 hours for 3-hr infusion groups and rises at 6 and 18 hour for 24-hr infusion groups. Viscous parameter C rises at 6, 12 hours and goes down for 3-hr group. FE results show that relaxation modulus at cytoplasm changes with the decreasing of paclitaxel concentration while that of the nucleus remains unchanged. From the stress-strain results, the Young’s moduli of the cytoplasm are lower than that of control groups for both 3-hr and 24-hr infusion groups, it implies that cytoplasm gets softer after treated by paclitaxel. At nucleus, the stiffness rises at 12 hours for the 3-hr infusion groups and rises from 6 to 18 hour for the 24-hr groups. In conclusion, both stiffness and viscous properties have larger changes in the 3-hr infusion group than the 24-hour group, suggesting that the cells were damaged more severely due to short time infusion dosing schedule. The soften of paclitaxel treated cytoplasm is consistent with the fact that paclitaxel would disrupt the microtubules of the cell. FE simulation results suggest that, regarding the peak indentation force, the axisymmetric model yield similar results as that of the full 3D model, saving the computation effort very much.
Key words: Biomechanics, paclitaxel, CIPN, quasi-linear viscoelastic theory, finite element method, 3D model reconstruction, AFM, confocal microscope

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