1,721,071 research outputs found
Molecular profiling for predicting tumor prognosis, treatment outcome and progression of squamous cell carcinoma
No full textSquamous cell carcinoma is the most common histological tumor type in the cervix uteri and oral tongue. Although both cancers are diagnosed at an early stage in the majority of cases, cervical cancer has a better prognosis despite similarities in treatment. The aim of this thesis is to increase our knowledge of tumor progression in squamous cell carcinoma at the molecular level, and to use this knowledge to explore the clinical implications of this knowledge in the development of therapeutic regimens.We collected archived tissues from squamous cell carcinoma of the cervix uteri and oral tongue (OTSCC) and applied immunohistochemistry (IHC), DNA cytometry and fluorescence in situ hybridization (FISH) to paraffin‐embedded tissues.Proliferative activity and genomic instability are two important factors in tumor progression. To identify patients with a high risk for locoregional recurrences we investigated Ki‐67 expression (by means of IHC) and DNA ploidy (using DNA image cytometry) in 76 pretreatment OTSCC biopsy specimens. We found Ki‐67 expression to be associated with an increased risk for locoregional recurrence in surgically‐treated Stage I cancer patients (P=0.028). Ninety‐seven percent of OTSCC specimens were aneuploid.Overexpression of epidermal growth factor receptor (EGFR) is associated with poor prognosis in head and neck cancer, but information on EGFR status in OTSCC is limited. We analyzed EGFR protein expression (IHC) and gene copy number (FISH) in 78 pretreatment OTSCC samples. We found EGFR gene copy numbers to be significantly associated with EGFR protein expression (P=0.002). EGFR was overexpressed in all OTSCC, suggesting that patients with this cancer type may benefit from EGFR targeting treatment. Non‐smokers showed higher EGFR gene copy numbers and protein overexpression than did smokers.The presence of lymph node metastases is a strong prognostic factor in early stage cervical cancer and OTSCC. LAMP3, PROX1, PRKAA1 and CCND1 are genes associated with carcinogenesis. We analyzed these gene copy numbers using FISH probes in pretreatment cervical biopsies from LN positive and LN negative Stage IB‐IIA cervical cancer patients (N=31) to explore their role in predicting LN metastasis. A combined marker panel consisting of amplified probes for LAMP3, PROX1 and PRKAA1 provided a significant (P=0.001) predictor for LN metastasis and needs to be evaluated in larger studies.To further explore genetic alterations in OTSCC, and inspired by the association between smoking habits and EGFR gene copy numbers, we applied five FISH probe markers (TERC, CCND1, EGFR, p53, CEP®4) to 65 pretreatment OTSCC specimens. CCND1 displayed the highest copy number of all markers and highest levels of this gene correlated significantly with better prognosis in Stage II OTSCC (P=0.03). Non‐smoking habits were significantly related to higher copy numbers in all five markers (P=0.002).List of scientific papersI. Wangsa D, Ryott M, Avall-Lundqvist E, Petersson F, Elmberger G, Luo J, Ried T, Auer G, Munck-Wikland E (2008). Ki-67 expression predicts locoregional recurrence in stage I oral tongue carcinoma. Br J Cancer. 99(7): 1121-8. Epub 2008 Sep 2 https://pubmed.ncbi.nlm.nih.gov/18766188II. Ryott M, Wangsa D, Heselmeyer-Haddad K, Lindholm J, Elmberger G, Auer G, Lundqvist EV, Ried T, Munck-Wikland E (2009). EGFR protein overexpression and gene copy number increases in oral tongue squamous cell carcinoma. Eur J Cancer. Mar 28: Epub ahead of print https://pubmed.ncbi.nlm.nih.gov/19332367III. Wangsa D, Heselmeyer‐Haddad K, Ried P, Eriksson E, Schäffer AA, Morrison LE, Luo J, Auer G, Munck‐Wikland E, Ried T, Åvall Lundqvist E (2009). FISH markers for detection of cervical lymph node metastases. [Submitted]IV. Wangsa D, Ryott M, Elmberger G, Schäffer AA, Auer G, Åvall Lundqvist E, Munck‐Wikland E, Ried T, Heselmeyer‐Haddad K (2009). Multiple FISH markers in oraltongue squamous cell carcinoma. [Manuscript]</p
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
Abstract 1438: The dynamics of genetic aberrations in Crohn's disease associated colorectal carcinogenesis
No full textAbstract
Crohn’s disease, a condition of chronic inflammation of the intestine, significantly increases the risk for the development of colorectal cancer (CRC). Sporadic CRCs are characterized by a specific pattern of genomic imbalances and a landscape of acquired gene mutations. In this study we aimed to compare CRCs that arise as a consequence of chronic inflammation in Crohn’s disease with sporadic CRCs.
We analyzed 26 Crohn’s disease associated CRCs, four matched dysplastic lesions, six matched inflamed mucosa samples, and two matched lymph node metastases using array comparative genomic hybridization, targeted sequencing (564 cancer related genes) and gene expression profiling. As a control, we used normal intestinal mucosa from the resection margin of these CRCs and 24 sporadic CRCs.
In general, CRCs that developed in patients with Crohn’s disease had a similar distribution of genomic imbalances compared to sporadic CRC. However, we identified distinct mutation signatures: in the Crohn's disease associated CRCs the most frequently mutated gene was TP53, which occurred in 65% of the samples. The second, third and fourth most frequently mutated genes were KRAS (27%), APC (23%) and PIK3CA (19%). In the control group of sporadically arising CRCs, the most commonly mutated gene was APC (75%), followed by KRAS (54%), TP53 (33%), SMAD3 (29%) and SMAD2 (25%). The genetic analyses of multiple lesions from individual patients revealed a high degree of intertumoral heterogeneity with diverse patterns of gene mutations and allowed the reconstruction of the sequence of genetic events during Crohn’s disease associated tumorigenesis. In contrast to sporadic colorectal carcinogenesis, TP53 mutations were observed as early and common events while APC mutations occurred rather late and were infrequent.
Our comprehensive molecular profiling of Crohn’s disease associated CRCs suggests that the genetic landscape of CRC is influenced by the activation of inflammation related pathways. Furthermore, our findings offer potential for establishing an early detection marker for dysplasia in patients with Crohn’s disease.
Citation Format: Daniela D. Hirsch, Darawalee Wangsa, Yue Hu, Jack Zhu, David Petersen, Daniel C. Edelman, Paul S. Meltzer, Bao Tran, Kerstin Heselmeyer-Haddad, Thomas Ried, Timo Gaiser. The dynamics of genetic aberrations in Crohn's disease associated colorectal carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1438. doi:10.1158/1538-7445.AM2017-1438</jats:p
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
- …
