1,720,986 research outputs found
Abstract IA06: Colorectal cancer in inflammatory bowel disease
No full textAbstract
Inflammatory bowel disease (IBD), consisting mainly of ulcerative colitis and Crohn's disease (CD), is characterized by chronic inflammation of the colon (and in the case of CD, other parts of the GI tract). As such, it is often considered the prototypical model of inflammation-associated carcinogenesis. After the well-known genetic syndromes that greatly predispose individuals to colorectal cancer (CRC), such as Lynch Syndrome and familial adenomatous polyposis (FAP), IBD is considered the third most common cause of high-risk CRC. Curiously, colitis-associated CRC (so-called CAC) shares several clinicopathological features with Lynch syndrome: CACs tend to affect young individuals, are often multifocal and/or affect the proximal colon, and frequently display mucinous and signet ring cell histology. Yet, to date, despite the identification of over 200 susceptibility genes for IBD itself, a germline genetic basis for human CAC has not been found.
Recent studies suggest that the overall incidence of CAC is decreasing in recent years. Although the reasons are not known, this is likely due to a combination of better identification of dysplasia due to enhanced imaging technology, better removal of preneoplastic lesions, perhaps better control of inflammation with newer IBD medications, and possibly earlier surgery before CAC has a chance to develop.
IBD itself is believed to occur in a genetically susceptible individual who gets exposed to certain environmental factors that trigger a chronic, often relentless, immune response. The paradigm for colorectal carcinogenesis in IBD holds that normal colorectal mucosa becomes exposed to an environmental insult (for example, following an intestinal infection, heavy use of NSAIDs, other unknown toxin), which, rather than resulting in restitution of normal colorectal health, develops into uncontrolled, chronic inflammation. After many years, and what is thought to be a recurring process of inflammation-induced cell proliferation and DNA damage, dysplasia and eventually cancer may arise.
Several lines of clinical evidence support the role of chronic inflammation in CAC. Risk increases with greater severity of colonic inflammation (whether measured histologically or endoscopically), greater extent of colon involvement, and longer duration of disease. And for unclear reasons, the 7-8% of patients with IBD who have concomitant chronic inflammation of the intra- and extra-hepatic bile ducts (primary sclerosing cholangitis) are at the highest risk of CAC. However, there are several clinical observations that pose challenges to the simple dogma that inflammation begets CAC. For example, individuals with chronic proctitis, in whom only the rectum has been inflamed for many years, are at no greater risk of rectal cancer than the general population. Also, patients with IBD-PSC while being at the greatest risk of CAC, typically have very quiescent colitis with minimal inflammation. And, one would expect that suppressing inflammation with IBD medications over the years should lower the risk of CAC, yet this has not been easy to prove, and many patients who get CAC have been on longstanding anti-inflammatory and immune modulating medications.
Like sporadic CRC, CAC arises from a dysplastic precursor lesion. The finding of a dysplastic lesion in a patient with IBD is perhaps the most important risk factor for future development of CAC. For the most part, the same genetic alterations that occur in the progression of sporadic adenomas to carcinoma also occur in CAC carcinogenesis. Some of the more important alterations occur with different frequency and different sequence between the two types of CRC. Most notably, APC mutations and LOH are early and very frequent in sporadic CRC but later and less frequent in CAC. Conversely, p53 alterations occur very early in CAC development, even in mucosa that is not frankly dysplastic, compared to sporadic carcinogenesis where it is often altered in later stage adenomas. Two recent studies conducted comprehensive analyses of genomic alterations in CAC compared to data from sporadic CRC reported by The Cancer Genome Atlas. Both studies confirmed the aforementioned observations of APC and p53. One of them also reported more frequent MYC expression in CAC, and rather unique expression of IDH1 in Crohn's-associated CAC (Yaeger et al.), and the other, more frequent mutation of SOX9 and EP300 (WNT pathway), NRG1 (ERBB ligand) and IL16 (Robles et al.). In the latter study, approximately one third of CACs showed alterations that might be targeted by new therapeutic agents (IDH1 R132; amplification of FGFR1, FGFR2, ERBB2, mutations encoding BRAF V600E, and EML4-ALK mutation). Recent studies have demonstrated proof of concept that analysis of altered tumor-associated DNA in stool of patients with IBD may be a useful adjunct to the clinical management of neoplasia risk.
To help sort out the role of various components of the immune system in CAC a large variety of animal models have been studied. For the most part, these models apply an inflammatory insult (DSS) with and without a carcinogen (AOM) in otherwise immune-intact mice, or in genetically modified mice with various cytokines or immune cell populations altered. These studies have elucidated many important mechanisms of inflammation-associated colon carcinogenesis, including the important observation that some animal models do not develop CAC in germ free environments but only do so in response to reintroducing commensal microbiota.
It is hoped that by applying knowledge from animal models, cellular and organoid systems, cancer stem cell biology, and further human/translational investigations, a better understanding of CAC development and treatment will emerge.
References
Beaugerie L, Itzkowitz SH. Cancers complicating inflammatory bowel disease. N Engl J Med. 2015 Apr 9;372(15):1441-52
Ullman TA, Itzkowitz SH. Intestinal inflammation and cancer. Gastroenterology. 2011 May;140(6):1807-16
Kisiel JB, Yab TC, Nazer Hussain FT, et al. Stool DNA testing for the detection of colorectal neoplasia in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2013 Mar;37(5):546-54
Robles AI, Traverso G, Zhang M, et al. Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease-Associated Colorectal Cancers. Gastroenterology. 2016 Apr;150(4):931-43
Yaeger R, Shah MA, Miller VA, et al. Genomic Alterations Observed in Colitis-Associated Cancers Are Distinct From Those Found in Sporadic Colorectal Cancers and Vary by Type of Inflammatory Bowel Disease. Gastroenterology. 2016 Aug;151(2):278-287
Citation Format: Steven Itzkowitz. Colorectal cancer in inflammatory bowel disease. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA06.</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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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