Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/20192
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dc.contributor許美鈴zh_TW
dc.contributorMeei-Ling Sheuen_US
dc.contributor.author陳怡靜zh_TW
dc.contributor.authorChen, Yi-Chingen_US
dc.contributor.other生物醫學研究所zh_TW
dc.date2012en_US
dc.date.accessioned2014-06-06T07:12:06Z-
dc.date.available2014-06-06T07:12:06Z-
dc.identifierU0005-2407201218224800en_US
dc.identifier.citationAy MR & Sarkar S. Computed Tomography Based Attenuation Correction in PET/CT: Principles, Instrumentation, Protocols, Artifacts and Future Trends. Iran J Nucl Med. 1-29 (2007). Bartlett JB, Dredge K & Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer. 4, 314-22 (2004). Birkenmerier, EH. et al. Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein. Genes Dev. 3, 1146-56 (1998). Calabrese L & Fleischer AB. Thalidomide: Current and Potential Clinical Applications. Am J Med. 108, 487-95 (2000). Cook KM & Figg WD. Angiogenesis Inhibitors-Currents Strategies and Future Prospects. CA Cancer J Clin. 60, 222-43 (2010). D’AMATO, R.J. et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci. 91, 4082-85 (1994). Ding YC. et al. uPA expression of gastric cancer cell lines and its correlation with peritoneal seeding. Zhonghua Zhong Liu Za Zhi. 27, 13-5 (2005). Dreyer C. et al. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell 68, 879-87 (1992). Fajas L, Debril MB & Auwerx J. Peroxisome proliferator-activated receptor-gamma: from adipogenesis to carcinogenesis. J Mol Endocrinol. 27, 1-9 (2001). Fawcett TW. et al. Physical and Functional Association between GADD153 and CCAAT/enhancer-binding Protein b during Cellular Stress. J Biol Chem. 271, 14285-9 (1995). Glass JD. et al. Very early activation of m-calpain in perheral nerve during Wallerian degeneration. J Neurol Sci. 15, 9-20 (2002). Grommes C, Landreth GE & Heneka MT. Antineoplastic effects of peroxisome proliferator-activated receptor gamma agonists. Lancet Oncol. 5, 419-29 (2004). Henning R. et al. Thalidomide Induces Apoptosis in Human Monocytes by Using a Cytochrome c-Dependent Patheay. J Immunol. 172, 5103-9 (2004). Ido T. et al. Labeled 2-deoxy-D-gulcose analogs. 18F-labeled 2-deoxy-2 flroro-D-glucose, 2-deoxy-2-fluoro-D-mannose and 14C-2-deoxy-2fluoro-D-glucose. JLCR. 14, 175-183 (1978). Issemann I. & Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347, 645-650 (1990). James GF & Timothy CW. Inflammation, atrophy, and gastric cancer. J Clin Invest. 117, 60-9 (2007). Johnson PF & McKnight SL. Eukaryotic transcriptional regulatory proteins. Annu Rev. Biochem. 58, 799-839 (1989). Kim MH & Fields J. Translationally regulated C/EBP beta isoform expression upregulates metastatic genes in hormone-independent prostate cancer cells. Prostate 68, 1362-71 (2008). Knobloch J. et al. Thalidomide Induces Limbs Anomalies by PTEN Stabilization, Akt Suppression, and Stimulation of Caspase-Dependent Cell Death. Mol Cell Biol. 28, 529-38 (2008). Kpmorowski J. et al. Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA.hy 926 cells. Life Sci. 78, 2558- (2006). Kupina NC. et al. The novel calpain inhibitor SJA6017 improves functional outcome after delayed administration in a mouse model of diffuse brain injury. J Neurotrauma. 18, 1229-40 (2001). Landschulz,WH. et al. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 2, 786-800 (1988). Lebrin F. et al. Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. Nat Med. 16, 420-8 (2010). Leung,W.K. Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 9, 279-87 (2008). Li X. et al. Thalidomide down-regulates the expression of VEFG and bFGF in cisplatin-resistant human lung carcinoma cell. Anticancer Res. 23, 2481-7 (2003). Lubisch W. et al. Benzoylalanine-Derived ketoamides carrying vinylbenzyl amino residues: discovery of potent water-soluble calpain inhibitors with oral bioavailability. J Med Chem. 46, 2404-12 (2003). McCullough KAREN D. et al. Gadd153 Sensitizes Cells to Endoplasmic Reticulum Stress by Down-Regulating Bc12 and Perturbing the Cellular Redox States. Mol Cell Biol. 21,1249-59 (2001). McMillin DW. et al. Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity. Nat Med. 16, 483-9 (2010). McKnight SL, Lane MD & Gluecksohn-Waelsch S. Is CCAAT/enhancer-binding protein a central regulator of energy metabolism? Genes Dev. 3, 2021-4 (1989). Nerlov C. The C/EBP family of transcription factors: a paradigm for interaction between gene expression and proliferation control. Trends Cell Biol. 17, 318-24 (2007). Nimmrich V. et al. Inhibition of calpain prevents NMDA-induced cell death and beta-amyloid-induces synaptic dysfunction in hippocampal slice cultures. Br J Pharmacol. 159, 1523-31 (2010). Ohno S. et al. Evolutionary origin of a calcium-dependent protease by fusion of genes for a thiol protease and a calcium-binding protein. Pernille Rorth. Nature 312, 566-70 (1984). Panigrahy D. et al. PPARgamma as a therapeutic target for tumor angiogenesis and metastasis. Cancer Biol Ther. 4, 687-93 (2005). Pernille R & Denise JM. Drosophila C/EBP: a tissue-specific DNA-binding protein requireo for embryonic development. Genes Dev. 6, 2299-2311 (1992). Regalo G. et al. C/EBPbeta is over-expressed in gastric carcinogenesis and is associated with COX-2 expression. J Pathol. 210, 398-404 (2006). Staiger J. et al. C/EBPbeta regulates body composition, energy balance-related hormones and tumor growth. Carcinogenesis. 30, 832-40 (2009). Storr SJ. The calpain system and cancer. Nat Rev Cancer. 11, 364-74 (2011). Suzuki K. et al. Structure, activation, and biology of calpain. Diabete. 53, S12-18 (2004). Verheul HM. et al. Combination oral antiangiogenic therapy with thalidomide and sulindac inhibits tumour growth in rabbits. Br J Cancer. 79, 114-8 (1999). Wang KK. et al. An alpha-mercaptoacrylic acid derivative is a selective nonpeptide cell-permeable calpain inhibitor and is neuroprotective. Proc Natl Acad Sci U S A. 93, 6687-92 (1996). Zhao R. et al. Vascular endothelial growth factor (VEGF) enhances gastric carcinoma invasiveness via integrin alpha beta6. Cancer Lett. 287, 150-6 (2010). Zhu DM & Fatih MU. Calpain Inhibitor II Induces Caspase-dependent Apoptosis in Human Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma Cells as Well as Some Sloid Tumor Cells. Clin Cancer Re. 6, 2456-63 (2000).en_US
dc.identifier.urihttp://hdl.handle.net/11455/20192-
dc.description.abstractBackground 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.en_US
dc.description.abstract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。 結論:1.以臨床用正子電腦斷層掃描影像評估應用於生物醫學基礎研究偵測癌細胞在小鼠體內的生長代謝是可行的。2.腹腔注射沙利竇邁可有效抑制胃癌轉移,此顯示在胃癌治療上是具有潛力的抗癌藥物。zh_TW
dc.description.tableofcontents中文摘要…………………………………………………………….i 英文摘要……………………………………………………………….ii 目次………………………………………………………………....iii 圖目次…………………………………………………………...vi 縮寫表………………………………………………………………...vii 第一章 緒論……………………………………………………..1 1. 正子電腦斷層掃描…………………….…………………........1 1.1 成像原理……………………..……………………………...1 1.2 臨床應用…………..………………………………………...1 2. 氟化去氧葡萄糖(FDG)……………….…………………………1 3. 胃癌………………………………………………………………2 3.1 流行病學………………………….………………………….2 3.2 臨床治療…………………………….………………………….3 4. 鈣蛋白酶 (Calpain)……………..…………………………….3 4.1 Calpain family…………………………………………………3 4.2 Calpain I 的功能…………………………………………3 4.3 Calpain I 與癌症……………………………………………4 5. C/EBPβ(CCAAT-enhancer-binding protein β)………………4 5.1 C/EBPβfamily…………………………………….4 5.2 C/EBPβ的功能……………………………………….4 5.3 C/EBPβ與癌症…………………….…………………………5 6. PPARγ(Peroxisome proliferator- activated receptor gamma)5 6.1 PPARγfamily……………….……………………….5 6.2 PPARγ的功能………………….…………………………….5 6.3 PPARγ與癌症…………….…………………………………….5 7. 內質網壓力 …………………………………………….5 7.1 內質網壓力……………….………………………………….5 7.2 內質網壓力與癌症…………….…………………………….5 8. 沙利竇邁(Thalidmoide)……………………………………….6 9. 研究方向及動機………………………………………………………6 9.1 基礎實驗 ……………………………………………………….6 9.2 分子影像實驗………………………………………………….7 第二章 材料與方法 ………..………………………………………...8 1. 實驗儀器……….…………………………………..……………...8 1.1 基礎實驗 ………………………….…………………………….8 1.2 分子影像實驗……………………….………………………….8 2. 實驗材料…………………………..………………………........8 2.1 基礎實驗 ………………………….…………………………….8 2.2 分子影像實驗……………….………………………………….8 3. 實驗方法………………………………………..……….………...8 3.1 基礎實驗 ………………………….………………………….8 3.2 分子影像實驗………………….………………………….11 第三章 實驗結果 …………………………………………………………...15 1. 臨床用正子電腦斷層掃描可應用於小鼠的偵測………………...15 2. 口服方式給予示蹤劑可取代尾靜脈注射方式………….……...15 3. 給予示蹤劑後第四個小時為小鼠造影之最適時機……….……16 4. 臨床用正子電腦斷層掃描可有效監控小鼠體內之腫瘤生長……16 5. 胃癌細胞株(MKN45)於小鼠體內生長所需最低細胞數量為5x10..16 6. Thalidomide 有效延緩胃癌細胞在裸鼠體內的生長 …………16 7. Thalidomide有效降低C/EBPβ、PPARγ及COX2在胃癌細胞內蛋白表現量……… 17 8. Thalidomide可誘導胃癌細胞內質網壓力的形成……………….17 9. Thalidomide可誘導內質網壓力的形成在胃癌腫瘤組織的表現.18 10. Thalidomide透過活化CalpainI,促使C/EBPβ在細胞內之表現降低…………18 11. Thalidomide有效抑制胃癌細胞腹膜轉移的現象………………18 12. Thalidomide降低VEGFR2、ERK及uPAR在胃癌細胞中的表現..…19 13. Thalidomide可降低基質金屬蛋白酶(MMP)的表現及活性……..19 14. 臨床用正子電腦斷層掃描可架構為抗腫瘤藥物的篩選平台.20 15. 臨床用正子電腦斷層掃描可運用於癌變過程監控平台………..20 16. 臨床用正子電腦斷層掃描可運用於原位癌化過程監控平台… 20 17.總結……………………………….…………………………...…20 第四章 討論 ………………………………………………………22 第五章 未來展望………………………………………………….....24 參考文獻…………………………………………………….…….….25 實驗結果圖表……………………………………………………….….29 附錄……………………………………….………………………..…58zh_TW
dc.language.isozh_TWen_US
dc.publisher生物醫學研究所zh_TW
dc.relation.urihttp://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2407201218224800en_US
dc.subject臨床用正子電腦斷層掃描zh_TW
dc.subjectClinical PET/CTen_US
dc.subject沙利竇邁zh_TW
dc.subjectThalidomideen_US
dc.title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zh_TW
dc.titleSequential FDG-PET/CT as a Biomarker of Response to Thalidomide in Peritoneal Gastric Cancer Dissemination in Miceen_US
dc.typeThesis and Dissertationzh_TW
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