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삼중음성유방암에 대한 니코틴아마이드의 항암 대사 기작에 관한 오믹스 연구
Get PDF학위논문(석사) -- 서울대학교대학원 : 자연과학대학 생명과학부, 2022. 8. 황대희.Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a poor prognosis. However, TNBC has been difficult to treat because it lacks specific target molecules. Therefore, a new therapeutic approach for TNBC is required. Nicotinamide (NAM) is a water-soluble amide derivative of niacin (vitamin B3) that plays an important role in mitochondrial metabolism and redox reactions. Previous studies have shown that NAM inhibits the growth and progression of various cancer cells, including TNBC. Here, we applied a multi-omics analytical approach to reveal the mechanistic link between NAM-induced metabolic regulation and the anti-tumor impact of NAM in TNBC. NAM decreased mitochondrial membrane potential and ATP production while increasing reverse electron transport (RET), fatty acid oxidation, and glycerophospholipid/sphingolipid metabolic pathways in TNBC, resulting in an increase in reactive oxygen species (ROS). The elevated levels of ROS initiated apoptosis and inhibited tumor development. Our findings revealed that NAM therapy causes cancer cell death in TNBC through mitochondrial malfunction and ROS activation via bifurcating metabolic pathways (RET and lipid metabolism). We propose that NAM supplement has a potential to be repositioned as a next-generation anti-metabolic agent for TNBC treatment, with the anticipation that our findings will pave the way for more advanced NAM use in clinical studies.삼중음성유방암(triple-negative breast cancer, TNBC)은 유방암의 분자학적 아형 중 가장 공격적이고 예후가 좋지 않은 아형이다. 그러나 TNBC는 타켓팅 할 수 있는 단백질이 없기 때문에 표적 치료법과 같은 방법을 사용할 수 없어 치료가 어렵다. 따라서 삼중음성유방암에 대한 새로운 치료 접근법이 필요하다. 니코틴아마이드(nicotinamide, NAM)는 미토콘드리아 대사 및 산화환원 반응에 중요한 역할을 하는 니아신(비타민 B3)의 수용성 아미드 유도체이다. 기존 연구에 의하면, 니코틴아마이드가 삼중음성유방암을 포함한 다양한 암세포의 성장과 진행을 억제하는 것으로 나타났다. 이 논문에서 우리는 니코틴아마이드 처리시 조절되는 세포의 대사과정과 삼중음성유방암에 대한 니코틴아마이드의 항암 효과 사이의 구체적인 연관성을 밝히기 위해 멀티오믹스 분석 접근법을 적용했다. 니코틴아마이드는 미토콘드리아 막 전위 및 아데노신삼인산 (ATP) 생성을 감소시키고, 삼중음성유방암에서 역전자전달(reverse electron transport, RET), 지방산 산화, 글리세로인지질/스핑고지질 대사 과정을 증가시켜 활성산소종(reactive oxygen species, ROS)을 증가시켰다. 높은 수준의 활성산소종은 세포사멸을 유도하고 암세포 발달을 억제한다고 알려져 있다. 이 논문에서는 니코틴아마이드가 삼중음성유방암에서 미토콘드리아 오작동을 통한 암세포 사멸을 유발하고, 크게 두가지 갈래의 물질대사(RET 및 지질 대사)를 조절하여 과도한 활성산소종 생성을 유발한다는 것을 밝혀냈다. 우리는 니코틴아마이드가 삼중음성유방암 치료를 위한 차세대 항암제로서의 잠재력이 있음을 제안하며, 나아가 이 연구가 니코틴아마이드가 임상연구에 보다 적극적으로 활용되는 기반을 마련할 것임을 기대한다.Chapter 1. Introduction 1
1.1 Study Background 1
1.2 Purpose of Research 2
Chapter 2. Methods 3
2.1 Cell culture and chemicals 3
2.2 RNA isolation, library preparation and sequencing 3
2.3 Transcriptomic analysis 4
2.4 Sample preparation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) 5
2.5 Proteomic data processing and analysis 6
2.6 Gene ontology annotation enrichment analysis 7
2.7 Reconstruction of molecular network models for DEGs and DEPs 8
2.8 Analysis of mRNA-seq data from TCGA breast cancer cohort 8
2.9 Measurement of mitochondrial membrane potential 9
2.10 Oxygen consumption rate (OCR) and real-time ATP rate analysis 10
2.11 Measurement of NAD+/NADH ratio 11
2.12 Quantification of Intracellular ROS 11
2.13 Cell viability assay 11
2.14 Flow cytometry analysis 12
2.15 Quantitative real-time polymerase chain reaction (qPCR) and qPCR array 13
2.16 Western blotting 13
Chapter 3. Results 15
3.1. Transcriptomic analysis showed that NAM inhibits mitochondrial activity by RET-mediated ROS generation 15
3.2. Proteogenomic analysis identified NAM induced alteration of lipid metabolism and apoptosis 24
3.3. NAM-induced metabolic alterations in proteogenomic networks converged on ROS generation and ROS-mediated apoptosis in TNBC 30
3.4. NAM induced mitochondrial dysfunction and ROS-mediated apoptosis in TNBC 36
Chapter 4. Discussion 42
Chapter 5. Conclusion 49
Bibliography 50
Abstract in Korean 55석
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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