1,720,961 research outputs found
Establishment and Characterization of A Multidrug Resistant (MDR) Colon Carcinoma Cell line and MDR Tumor Model in BALB/c Mice
No full text過度表現多重藥物抗藥性mdr1基因為癌症病患主要化療失敗的原因之一，mdr1基因產物為細胞膜上之轉運蛋白P-glycoprotein (P-gp)，此蛋白將化療藥物從腫瘤細胞中排出因此無法有效毒殺腫瘤細胞。本論文的研究目的為建立具有抗藥性的腫瘤細胞株及其小鼠腫瘤動物模式，以應用於抗藥性腫瘤之研究。大腸癌CT-26/WT細胞株逐漸式培養在doxorubicin (DOX)濃度由低至高(1 nM-1 μM或10 μM)後，稱此為CT-26/DOX1和CT-26/DOX10亞型細胞株，以MTT試驗測試細胞對化療藥物的抗藥性，結果顯示CT-26/DOX1細胞對於DOX的抵抗倍率(resistant index; RI)相較於CT-26/WT為90倍，對P-gp基質之化療藥物vincristine和etoposide的RI也高於CT-26/WT，而對非P-gp基質之化療藥物5-FU和methotrexate，其RI則與CT-26/WT相似。CT-26/DOX1細胞在mdr1a mRNA表現較CT-26/WT高，而其他抗藥性基因mdr1b和mrp1表現則無差異。在P-gp蛋白表現和功能方面，CT-26/DOX1和CT-26/DOX10細胞顯著高於CT-26/WT。將細胞皮下接種於小鼠，於CT-26/WT和CT-26/DOX1活體腫瘤大小約75-250 mm3時，給予三劑DOX化療，CT-26/DOX1腫瘤大小相較於CT-26/WT有極顯著較高，老鼠犧牲後萃取其腫瘤的RNA和蛋白質，CT-26/DOX1腫瘤之mdr1a mRNA表現高於CT-26/WT，mdr1b和mrp1 mRNA則無差異。CT-26/DOX1腫瘤的P-gp表現亦高於CT-26/WT。而CT-26/WT和CT-26/DOX1腫瘤的病理特徵皆屬高度侵犯性和異型性，且血管充份供應。綜合上述結果證實本研究已建立抗藥性大腸癌CT-26/DOX1和CT-26/DOX10的細胞模式以及CT-26/DOX1的實驗動物模式。此抗藥性活體模式以核醫影像和自體放射性顯影，利用示蹤劑99mTc-MIBI診斷P-gp功能並無法測得影像，99mTc-MIBI 在CT-26/WT和CT-26/DOX1腫瘤分布量極低，但腫瘤對18F-FDG的攝取則非常清晰，未來可嘗試利用其他示蹤劑如99mTc-tetrofosmin、18F-paclitaxel和11C-verapamil等以進行抗藥性活體動物的影像分析。目錄
誌謝-------------------------------------------------------------------------------------------- Ⅰ
中文摘要-------------------------------------------------------------------------------------- Ⅱ
Abstract --------------------------------------------------------------------------------------- Ⅲ
目錄-------------------------------------------------------------------------------------------- Ⅴ
圖次-------------------------------------------------------------------------------------------- Ⅸ
表次-------------------------------------------------------------------------------------------- ⅩⅠ
簡寫對照表----------------------------------------------------------------------------------- ⅩⅡ
第一章、前言與文獻探討------------------------------------------------------------------ 1
第一節、多重藥物抗藥性(multidrug resistance；MDR)----------------------------- 1
一、MDR在臨床扮演之角色---------------------------------------------------------- 1
二、P-gp的構造、功能、分布及造成MDR的機制--------------------------------- 2
第二節、抗藥性腫瘤的細胞模式和實驗動物模式---------------------------------- 5
一、抗藥性腫瘤的細胞模式----------------------------------------------------------- 5
二、抗藥性腫瘤的實驗動物模式----------------------------------------------------- 6
第三節、MDR抑制物(modulators；inhibitors) ---------------------------------------- 6
一、P-gp抑制物(modulators; inhibitors)在臨床上的療效評估------------------ 6
二、天然的P-gp modulators------------------------------------------------------------ 8
第四節、臨床上診斷P-gp的策略------------------------------------------------------- 10
一、傳統診斷MDR之方法------------------------------------------------------------ 10
二、非侵入性核子醫學影像技術----------------------------------------------------- 10
三、核醫影像偵測P-gp之功能------------------------------------------------------- 11
四、99mTc-MIBI在抗藥性腫瘤動物模式造影之研究---------------------------- 12
第五節、研究動機與目的---------------------------------------------------------------- 13
第二章、實驗材料與方法------------------------------------------------------------------ 14
第一節、藥品資料------------------------------------------------------------------------- 14
第二節、實驗方法------------------------------------------------------------------------- 15
一、細胞株及動物模式----------------------------------------------------------------- 15
二、建立抗藥性細胞株之流程-------------------------------------------------------- 15
三、利用MTT測定化療藥物對細胞之毒殺作用---------------------------------- 17
四、Trypan Blue染色比較CT-26/WT和CT-26/DOX1細胞株之生長曲線 17
五、Flow cytometry分析P-gp表現--------------------------------------------------- 18
六、以calcein-AM分析細胞P-gp功能---------------------------------------------- 18
七、以rhodamine123 (Rh123)分析細胞P-gp功能--------------------------------- 19
八、建立抗藥性CT-26腫瘤動物模式之流程-------------------------------------- 19
九、反轉錄-聚合酶鏈反應(RT-PCR)------------------------------------------------- 20
十、Western blot分析P-gp表現------------------------------------------------------- 23
十一、腫瘤組織之蘇木紫-伊紅(hematoxylin-eosin; H&E)染色----------------- 24
十二、腫瘤組織P-gp和血管之免疫組織化學(Immunohistochemistry；IHC)染色---------------------------------------------------------------------------------------
26
十三、偵測99mTc-MIBI在腫瘤之分布----------------------------------------------- 27
Ι、閃爍攝影機(scintigraphy)活體偵測腫瘤分布------------------------------ 27
Ⅱ、自體放射性顯影(autoradiography)偵測腫瘤分步------------------------ 28
十四、利用PET活體影像18F-FDG在腫瘤之分布-------------------------------- 28
十五、數據統計分析-------------------------------------------------------------------- 29
第三章、實驗結果--------------------------------------------------------------------------- 30
第一節、探討抗藥性CT-26/DOX1及CT-26/DOX10細胞株之形態、生長速
度、抗化療藥物及抗藥性基因和蛋白表現-------------------------------------------
30
一、觀察CT-26/WT、CT-26/DOX1及CT-26/DOX10細胞之形態-------------- 30
二、CT-26/WT、CT-26/DOX1及CT-26/DOX10細胞之生長速度--------------- 30
三、DOX及其他化療藥物對CT-26/WT、CT-26/DOX1及CT-26/DOX1 n7細胞之毒殺作用------------------------------------------------------------------------
30
四、分析CT-26/WT、CT-26/DOX1細胞抗藥性(MDR)基因mRNA之表現 31
五、分析CT-26/WT、CT-26/DOX1及CT-26/DOX10細胞之P-gp表現-------- 32
Ι、Western blot分析P-gp表現---------------------------------------------------- 32
Ⅱ、Flowcytometry分析P-gp表現------------------------------------------------- 32
六、分析CT-26/WT、CT-26/DOX1及CT-26/DOX10細胞之P-gp功能-------- 33
Ι、Calcein-AM分析P-gp功能----------------------------------------------------- 33
Ⅱ、Rh123分析P-gp功能----------------------------------------------------------- 33
第二節、探討動物模式下抗藥性腫瘤之生長、抗藥性基因之表現以及CT-26腫瘤之病理特性---------------------------------------------------------------------------
44
ㄧ、給藥組及對照組老鼠之體重、腫瘤生長變化--------------------------------- 44
二、CT-26/WT、CT-26/DOX1活體腫瘤組織MDR基因之mRNA表現------- 44
三、H&E染色觀察CT-26/WT和CT-26/DOX1腫瘤之特性--------------------- 45
四、CT-26/WT、CT-26/DOX1活體腫瘤組織之P-gp表現---------------------- 45
Ι、Western blot----------------------------------------------------------------------- 45
Ⅱ、IHC染色法----------------------------------------------------------------------- 45
五、IHC染色觀察CT-26/WT和CT-26/DOX1腫瘤之血管分布---------------- 46
第三節、探討99mTc-MIBI和18F-FDG在此抗藥性腫瘤模式之研究-------------- 46
一、Scintigraphy偵測活體99mTc-MIBI在CT-26/WT和CT-26/DOX1腫瘤之分布------------------------------------------------------------------------------------
46
二、自體放射性顯影(autoradiography)偵測99mTc-MIBI在CT-26/WT和CT-26/DOX1腫瘤之分布-------------------------------------------------------------
46
三、18F-FDG在活體腫瘤之分布------------------------------------------------------ 46
第四章、討論--------------------------------------------------------------------------------- 58
第一節、抗藥性腫瘤細胞的建立------------------------------------------------------- 58
第二節、抗藥性腫瘤的實驗動物模式建立------------------------------------------- 62
第三節、探討99mTc-MIBI和18F-FDG在此抗藥性腫瘤模式之研究-------------- 63
參考文獻-------------------------------------------------------------------------------------- 6
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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