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구강 편평상피암 수술 후 예후에 있어 종양세포와 숙주면역의 예측생체지표들에 대한 연구
Get PDF학위논문 (석사)-- 서울대학교 대학원 : 의학과, 2014. 8. 안순현.서론: 구강 상피세포암은 세계적으로 발병률이 높은 악성종양 중 하나이다. 악성종양의 치료법이 발달했음에도 불구하고 지난 수 세기 동안 구강 상피세포암의 5년 생존율은 50% 수준을 유지하고 있다. 종양에 대한 TNM 분류법이 예후예측에 주로 사용되고 있으나 이분류법은 종양이 가지는 생물학적 특성이나 숙주의 종양 방어 면역 작용을 반영하지 못한다. mRNA Microarray를 사용한 종양세포의 생물학적 특징과 숙주 방어 면역 체계에 대한 이전 연구에서 예후와 관련이 깊을 것으로 보이는 9가지 생체지표를 찾았다. 그 중 5가지는 종양세포에서 발현되는 유전자이고 나머지 4개는 면역체계에서 발현되는 유전자이다. 본 연구에서는 면역조직화학염색법을 통해 생체지표의 예후 예측 정도를 확인해보고자 한다.
방법: 2003년부터 2011년까지 수술을 받은 모든 구강 상피세포암 환자를 대상으로 하였다. 총 69명의 종양조직과 60명의 종양조직이 침범이 없는 정상 경부임파선으로 Tissue Microarray를 구축하였다. 9개의 생체지표 중 FAS, HIF1-alpha, Bcl2A, MST4, ErbB3는 종양세포에 염색을 시행하였으며, STAG2, CD40L, CD80, PTPRO는 임파선에 염색을 시행하였다. 면역조직화학염색은 염색의 범위와 강도를 고려한 반정량적 점수계산법(H 점수)에 따라 등급을 나누었다. 면역조직화학염색 결과를 바탕으로 생체지표들을 임상병리학적 소견과 임상결과로 무재발, 무질병, 전체 생존율을 비교해 분석하였다.
결과: 총 69개의 케이스 중, 혀가 구강 상피세포암의 가장 다빈도 발생한 부위였다. 종양의TNM 분류 중에서는 제4기(33.3%)가 가장 흔했으며 그 다음으로는 제 1기(26.1%), 제 2기(26.1%), 제 3기(14.5%)가 있었다. 성공적인 종양절제에도 불구하고 수술 후 종양 재발률은 27.5%였다. TNM 제4기가 나쁜 생존률의 높은 위험요인으로 나타났다 (p < 0.001). 9가지의 생체지표들 중에서 FAS만이 TNM 분류와 강한 양의 상관관계를 나타내었다 (p = 0.019). 종양세포에서 FAS, HIF1-alpha, ErbB3의 양성발현이 종양의 재발과 유의성을 보였다 (p = 0.070, p = 0.070, p = 0.039). 임파선에서CD40L의 음성발현은 종양의 재발과 유의한 관계를 보였다 (p = 0.030). 다변수 Cox분석결과 종양세포에서 TNM 4기, HIF1-alpha의 H 점수 증가와 임파선에서 CD40L의 H점수 감소가 각각 독립적으로 무재발생존률에서 나쁜 예후를 보였다(p < 0.001, HR=6.990, 95% CI 2.361-20.70 for TNM 4기, p = 0.006, HR=1.020, 95% CI 1.006-1.034 for HIF1-alphap = 0.020, HR=0.978, 95% CI 0.960-0.996 for CD40L). 전체생존률에서는 HIF1-alpha의 H점수 증가, CD40L의 H점수 감소가 TNM 분류와 각각 독립적으로 나쁜 예후인자들로 나타났다. (p = 0.008, HR=1.024, 95% CI 1.007-1.042 for HIF1-alphap = 0.022, HR=0.973, 95% CI 0.950-7.996 for CD40L)
결론: 본 연구에서는 종양세포와 종양에 대한 숙주 방어 면역에서 각각 HIF1-alpha와 CD40L의 발현 정도가 구강 상피세포암의 수술 후 예후를 예측하는 생체지표로 사용될 수 있음을 확인하였다.Introduction: Oral squamous cell carcinoma (OSCC) is one of the common malignancies worldwide. While treatment modalities have been advanced, the five-year survival rate is about 50% in stationary for several decades. The TNM staging has been conventionally used to predict the prognosis but it does not give biological information of tumor cell and host immunity against tumor. Evaluating the biologic characteristics of the primary tumor and host immune defense system, our previous microarray analysis of mRNA found out 9 candidates of prognostic biomarkers5 for primary tumor tissue and 4 for host normal lymph nodes. This study aimed to evaluate the prognostic values of the biomarkers assessed by immunohistochemistry (IHC)
Methods: All patients with OSCC, who underwent successful surgical resections from January 2003 to December 2011, were included in this study. Tissue arrays were constructed for 69 primary tumor tissues and 60 normal cervical lymph nodes not affected by tumor. IHC of the nine candidates were applied to corresponding tissue arraysFAS, HIF1-alpha, Bcl2A, MST4, and ErbB3 to the primary tumors and STAG2, CD40L, CD80, and PTPRO to the lymph nodes. IHC was graded by semi-quantative histologic scoring system (H score) considering the extent and intensity of the staining. IHC results were correlated with clinicopathological characteristics and with clinical outcomes such as, relapse free, disease free, and overall survivals.
Results: In total 69 cases, Oral tongue was the most frequently affected primary site. In TNN staging, stage IV (33.3%) is most frequent followed by stage I (26.1%), II (26.1%), and III (14.5%). Despite of successful resection, there was 27.5% of recurrence. TNM stage IV was highly related with poor clinical outcomes (p < 0.001). Among the 9 biomarkers, the expression of FAS only showed strong positive correlation with the TNM staging (p = 0.019). The positive expression of FAS, HIF1-alpha, and ErbB3 in the tumor cells had correlation with recurrence (p = 0.070, 0.070, and 0.039 respectively). The negative expression of CD40L in the lymph nodes had significant positive correlation with recurrence (p = 0.030). The multivariate Cox regression showed that TNM staging and H score of HIF1-alpha in primary tumors were independent poor prognostic factors in the relapse free survival while H score of CD40L in the lymph nodes was good prognostic factor (p < 0.001, HR=6.990, 95% CI 2.361-20.70 for TNM stage IVp = 0.006, HR=1.020, 95% CI 1.006-1.034 for H score of HIF1-alphap = 0.020, HR=0.978, 95% CI 0.960-0.996 for H score of CD40L). In the overall survival, elevated H score of HIF1-alpha and decreased H score of CD40L were independent poor prognostic factors with TNM staging. (p = 0.008, HR=1.024, 95% CI 1.007-1.042 for HIF1-alphap = 0.022, HR=0.973, 95% CI 0.950-7.996 for CD40L).
Conclusions: The expressions of HIF1-alpha and CD40L, in the primary tumors and the normal lymph nodes respectively, could be used as postoperative prognostic biomarkers of tumor cell and host immunity against the tumor in OSCC.CONTENTS
Abstract ----------------------------- i
Table of Contents ------------------------ v
List of Tables and Figures ------------------ vii
List of Abbreviations ---------------------- ix
Introduction --------------------------- 1
Materials and Methods --------------------- 5
Results ------------------------------ 11
Discussion ---------------------------- 19
Conclusions --------------------------- 24
References --------------------------- 25
Abstract in Korean ----------------------- 65Maste
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
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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
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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
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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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