1,720,959 research outputs found
Bioinformatic approaches elucidate a high likelyhood of interaction between miR-182 and the pro-apoptotic gene MTCH2 in breast cancers
No full textMolecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease
Get PDFBackground: It is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin-fixed paraffin-embedded (FFPE) prostate biopsies from cohorts with post-radiotherapy (RT) long-term clinical follow-up has been limited. Utilizing parallel sequencing modalities, we performed a proof-of-principle sequencing analysis of historical diagnostic FFPE prostate biopsies. We compared patients with (i) stable PCa (sPCa) postprimary or salvage RT, (ii) progressing PCa (pPCa) post-RT, and (iii) de novo metastatic PCa (mPCa).
Methods: A cohort of 19 patients with diagnostic prostate biopsies (n = 6 sPCa, n = 5 pPCa, n = 8 mPCa) and mean 4 years 10 months follow-up (diagnosed 2009–2016) underwent nucleic acid extraction from demarcated malignancy. Samples underwent 3′RNA sequencing (3′RNAseq) (n = 19), nanoString analysis (n = 12), and Illumina 850k methylation (n = 8) sequencing. Bioinformatic analysis was performed to coherently identify differentially expressed genes and methylated genomic regions (MGRs).
Results: Eighteen of 19 samples provided useable 3′RNAseq data. Principal component analysis (PCA) demonstrated similar expression profiles between pPCa and mPCa cases, versus sPCa. Coherently differentially methylated probes between these groups identified ~600 differentially MGRs. The top 50 genes with increased expression in pPCa patients were associated with reduced progression-free survival post-RT (p < 0.0001) in an external cohort.
Conclusions: 3′RNAseq, nanoString and 850k-methylation analyses are each achievable from historical FFPE diagnostic pretreatment prostate biopsies, unlocking the potential to utilize large cohorts of historic clinical samples. Profiling similarities between individuals with pPCa and mPCa suggests biological similarities and historical radiological staging limitations, which warrant further investigation
Informed Consent, Biobank Research, and Locality: Perceptions of Breast Cancer Patients in Three European Countries
No full textComparative studies are missing that explore how socio-cultural and institutional circumstances influence patient comprehension and expectations regarding informed consent for current and future research on their tissue and data. This study compares how breast cancer patients in three European countries (the United Kingdom, Belgium, and Germany) who have consented to participate in tumor banking assess the given consent and the accompanying local contextual factors influencing it. Our survey demonstrates that only 59% of the patients in the British survey, but about 90% in the German and Belgian surveys, correctly recalled tissue and data donation for study purposes. Of those who remembered the study participation status correctly, about 90% had altruistic motives. At the same time, approximately half of the survey participants, or even 70% of the Belgians, expected personal benefit from research participation and information on cancer risk within the family. About half of the interviewees, but only 27% of the British participants, definitively wanted to be asked for re-consent for future research. Of the local contextual factors under study, participants’ appraisals of medical science and data protection were particularly pertinent. More culturally and contextually sensitive comparative research is needed to better understand patient attitudes toward research participation and tissue donation in the context of biobank research
Using functional and computational genomics approaches to study the cross-talk between radiosensitivity and HIF-1α activation
No full textRadiotherapy is believed to account for 40% of curative cancer treatment, yet ionising radiation (IR) resistance often ensues. Hypoxia, accompanied by HIF-1α pathway activation, is a known IR resistance mechanism. Studies have revealed ubiquitination’s crucial roles in DNA damage response and repair and IR response, but have only focused on a few ubiquitin-conjugating genes.
This thesis aimed to identify ubiquitin-conjugating genes involved in cellular response to IR following hypoxia-induced HIF-1α activation, that could present novel druggable targets to synergise with radiotherapy. Glioblastoma was used as a research model, as hypoxia has been shown to play an important role in GBM progression and treatment resistance. Additionally, GBM treatment relies on radiotherapy and surgery as there is a paucity of targeted GBM treatment.
In silico analysis identified multiple significant genes that impacted patient survival as well as a significant prognostic 15-gene signature in low grade glioma patients. Computational tools were used to analyse a pooled IR CRISPR-Cas9 screen utilising a focused ubiquitin-targeting library in GBM cells. Radiosensitivity was identified upon CCNF knockout from the screen and a novel cyclin F/EXO1 axis that controls double-stranded break repair was identified following experimental validation. A novel focused CRISPR-Cas9 screen using targeting the ubiquitin system and investigating radioresponse in hypoxic conditions in GBM cells was conducted. In silico identified radiation and hypoxia response genes as well as genes uniquely identified to be determinants of radioresponse in hypoxic conditions. Finally, an improved CRISPR-Cas9 library was designed for the investigation the ubiquitin system.
Together, these results and analyses highlight the role of the ubiquitin system in hypoxia and DNA damage responses in the context of cancer
Are Signatures of Radiosensitivity Ready for Routine Clinical Use? a Pragmatic Comparison of Clinical, Pathological and Gene Signature Predictors of Outcome in Oropharynx Head and Neck Cancers
Get PDFGoing 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
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