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標題: 以臨床用正子電腦斷層掃瞄系列影像為生物標誌評估沙利竇邁於小鼠胃癌腹膜擴散機制之探討
Sequential FDG-PET/CT as a Biomarker of Response to Thalidomide in Peritoneal Gastric Cancer Dissemination in Mice
作者: 陳怡靜
Chen, Yi-Ching
關鍵字: 臨床用正子電腦斷層掃描;Clinical PET/CT;沙利竇邁;Thalidomide
出版社: 生物醫學研究所
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Background and Purpose: A clinical positron emission tomography imaging (Postrion Emission Tomography/Computed Tomography Images) applied to the mice, a new architecture that combines the adjustment of the hardware and software on the construction of clinical positron emission tomography scanning can be applied to tumors in micedetection by the image showing the tumor cells to give the number of assessments and effective construction of a tumor suppressor effect of drug screening platform. In this paper, the use of drugs as thalidomide, thalidomide has been pointed out with anti-angiogenesis function, however, its mechanism has not yet fully clarify, in the basic experimental section, we use in vivo and in vitro tests to analyze and vascular newborn associated protein of PPAR-γ and transcription factors of the CEBP-β in the inhibition of metastasis of gastric cancer on the feasibility and mechanisms. And combined with the assessment of molecular imaging, in order to reduce the sacrifice mice in the experiment.
Methods: A total of four gastric cancer cell experiment, given first of all by the three different tracer to confirm the future of drug to give way. Then scanned using positron emission tomography assessment required to give the number of tumor cells, tumor cells in mice on growth of and monitoring by image, select the best given the time of the tumor suppressor drugs, re-use continuous video monitoring drug effects. Western blot and immunohistochemical staining of the tumor in nude mice peritoneal PPAR-γ and transcription factor of the CEBP-β expression.
Results: PPAR-γ and CEBP-β decreased expression in gastric cancer tissues and cells. The Salle sinus step is to influence the phosphorylation of the CEBP-β through the activation of Effect of Calpain I, reducing the expression of PPAR-γ and the CEBP-β, thereby inhibiting tumor metastasis. In addition, thalidomide effective inhibition of gastric cancer cells in peritoneal metastasis in nude mice, and in accordance with the results of image analysis.
Conclusions: 1. The clinical positron emission tomography imaging as a biomarker to detecte growth and metabolism of cancer cells in mice. 2. Thalidomide effectively inhibited the metastasis of gastric cancer, this show has potential anti-cancer drugs in the treatment of gastric cancer.

背景及目的:本文提出臨床正子電腦斷層影像( Postrion Emission Tomography/Computed Tomography Images)應用於實驗小鼠的新架構,此架構結合了硬體上的調整及軟體上的建構,使臨床用正子電腦斷層掃瞄可應用於小鼠腫瘤偵測上,藉由影像呈現進行腫瘤細胞給予定性質定量上的評估及有效建構一個抑癌藥物效果的篩選平台。下一段本文主要使用藥物為沙利竇邁(Thalidomide),沙利竇邁已有研究指出具有抗血管新生之功用,然而其機轉至今尚未完全釐清。因此在基礎實驗部分,我們利用體內及體外試驗來分析與血管新生相關蛋白 PPAR-γ及轉錄因子 CEBP-β 在抑制胃癌轉移上的可行性及其機轉。並同時結合分子影像的評估,以減少實驗過程中小鼠的犧牲。
實驗方法:共使用三株胃癌細胞(AGS、SCM-1、MKN45)進行實驗,首先藉由三種不同給予示蹤劑方式確認日後藥物給予方式。接著利用正子電腦斷層掃描評估所需給予腫瘤細胞數量,並藉由影像監控腫瘤細胞於小鼠體內成長情形,選取最佳給予抑癌藥物的時間點,再利用持續影像監控藥物之效果。西方點墨法及免疫組織化學染色法分析裸鼠腹膜內腫瘤組織 PPAR-γ 及轉錄因子 CEBP-β 的表現量。
實驗結果:PPAR-γ 及 CEBP-β 均於胃癌組織及細胞內降低表達。沙利竇邁乃透過活化 Calpain I 來影響CEBP-β 的磷酸化,降低 PPAR-γ 及 CEBP-β 的表現量,進而抑制腫瘤轉移。另外,於裸鼠體內試驗中也發現沙利竇邁可有效抑制胃癌細胞腹膜內的轉移,且符合影像分析結果。
其他識別: U0005-2407201218224800
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