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9. Reply

Author

Wassie, Molla M., primary, Young, Graeme P., additional, Winter, Jean M., additional, Cock, Charles, additional, and Symonds, Erin L., additional

Published
2024
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12. BCAT1, IKZF1 and SEPT9: methylated DNA biomarkers for detection of pan-gastrointestinal adenocarcinomas.

Author

Laven-Law, Geraldine, Kichenadasse, Ganessan, Young, Graeme P., Symonds, Erin L., and Winter, Jean M.

Subjects
ADENOCARCINOMA, DNA methylation, BIOMARKERS, DNA, CIRCULATING tumor DNA
Abstract

Methylated circulating tumour DNA (ctDNA) blood tests for BCAT1/IKZF1 (COLVERA) and SEPT9 (Epi proColon) are used to detect colorectal cancer (CRC). However, there are no ctDNA assays approved for other gastrointestinal adenocarcinomas. We aimed to characterize BCAT1, IKZF1 and SEPT9 methylation in different gastrointestinal adenocarcinoma and non-gastrointestinal tumours to determine if these validated CRC biomarkers might be useful for pan-gastrointestinal adenocarcinoma detection. Tissue DNA methylation data from colorectal (COAD, READ), gastroesophageal (ESCA, STAD), pancreatic (PAAD) and cholangiocarcinoma (CHOL) adenocarcinoma cohorts within The Cancer Genome Atlas were used for differential methylation analyses. Clinicodemographic predictors of BCAT1, IKZF1 and SEPT9 methylation, and the selectivity of hypermethylated BCAT1, IKZF1 and SEPT9 for colorectal adenocarcinomas in comparison to other cancers were each explored with beta regression. Hypermethylated BCAT1, IKZF1 and SEPT9 were each differentially methylated in colorectal and gastroesophageal adenocarcinomas. IKZF1 was differentially methylated in pancreatic adenocarcinoma. Hypermethylated DNA biomarkers BCAT1, IKZF1 and SEPT9 were largely stable across different stages of disease and were highly selective for gastrointestinal adenocarcinomas relative to other cancer types. Existing CRC methylated ctDNA blood tests for BCAT1/IKZF1 and SEPT9 might be usefully repurposed for use in other gastrointestinal adenocarcinomas and warrant further prospective ctDNA studies. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Using Research To Inform Business and Strategic Decisions.

Author

Young, Graeme

Abstract

This paper examines and reviews research techniques used to support business and strategic planning at a large metropolitan technical and further education (TAFE) college. Section 1 is an outline of the structure of Chisholm Institute's planning and research processes. It discusses the management structure, strategic plan, and departments within the strategy. Section 2 describes these four areas of research undertaken by staff in the Quality and Planning Department: analysis of internal and external databases, evaluation of program and services, market research/investigative activities, and trend monitoring and environmental scanning. Section 3 addresses benefits and shortcomings of the research techniques. It finds the internal database analysis enables analysis of primary data, but it is static and can only provide an analysis of previously captured information; external databases provide a wider picture of the student population, but may be difficult to drill down to a local level; evaluations of programs and services provide a measure of success of targets, but are dependent on their focus and extent; market/investigative research can provide answers on an issue, but can be costly in time and resources; and trend/environmental scanning allows access to a range of information sources, but the information obtained may not be applicable to local conditions. (YLB)

Published
2001

24. World Endoscopy Organization Consensus Statements on Post-Colonoscopy and Post-Imaging Colorectal Cancer

Author

Rutter, Matthew D., Beintaris, Iosif, Valori, Roland, Chiu, Han Mo, Corley, Douglas A., Cuatrecasas, Miriam, Dekker, Evelien, Forsberg, Anna, Gore-Booth, Jola, Haug, Ulrike, Kaminski, Michal F., Matsuda, Takahisa, Meijer, Gerrit A., Morris, Eva, Plumb, Andrew A., Rabeneck, Linda, Robertson, Douglas J., Schoen, Robert E., Singh, Harminder, Tinmouth, Jill, Young, Graeme P., and Sanduleanu, Silvia

Published
2018
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27. An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles

Author

Bresalier, Robert S, primary, Senore, Carlo, additional, Young, Graeme P, additional, Allison, James, additional, Benamouzig, Robert, additional, Benton, Sally, additional, Bossuyt, Patrick M M, additional, Caro, Luis, additional, Carvalho, Beatriz, additional, Chiu, Han-Mo, additional, Coupé, Veerle M H, additional, de Klaver, Willemijn, additional, de Klerk, Clasine Maria, additional, Dekker, Evelien, additional, Dolwani, Sunil, additional, Fraser, Callum G, additional, Grady, William, additional, Guittet, Lydia, additional, Gupta, Samir, additional, Halloran, Stephen P, additional, Haug, Ulrike, additional, Hoff, Geir, additional, Itzkowitz, Steven, additional, Kortlever, Tim, additional, Koulaouzidis, Anastasios, additional, Ladabaum, Uri, additional, Lauby-Secretan, Beatrice, additional, Leja, Mārcis, additional, Levin, Bernard, additional, Levin, Theodore Robert, additional, Macrae, Finlay, additional, Meijer, Gerrit A, additional, Melson, Joshua, additional, O'Morain, Colm, additional, Parry, Susan, additional, Rabeneck, Linda, additional, Ransohoff, David F, additional, Sáenz, Roque, additional, Saito, Hiroshi, additional, Sanduleanu-Dascalescu, Silvia, additional, Schoen, Robert E, additional, Selby, Kevin, additional, Singh, Harminder, additional, Steele, Robert J C, additional, Sung, Joseph J Y, additional, Symonds, Erin Leigh, additional, and Winawer, Sidney J, additional

Published
2023
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28. BCAT1, IKZF1and SEPT9: methylated DNA biomarkers for detection of pan-gastrointestinal adenocarcinomas

Author

Laven-Law, Geraldine, Kichenadasse, Ganessan, Young, Graeme P., Symonds, Erin L., and Winter, Jean M.

Abstract

AbstractIntroductionMethylated circulating tumour DNA (ctDNA) blood tests for BCAT1/IKZF1(COLVERA) and SEPT9(Epi proColon) are used to detect colorectal cancer (CRC). However, there are no ctDNA assays approved for other gastrointestinal adenocarcinomas. We aimed to characterize BCAT1, IKZF1and SEPT9methylation in different gastrointestinal adenocarcinoma and non-gastrointestinal tumours to determine if these validated CRC biomarkers might be useful for pan-gastrointestinal adenocarcinoma detection.MethodsTissue DNA methylation data from colorectal (COAD, READ), gastroesophageal (ESCA, STAD), pancreatic (PAAD) and cholangiocarcinoma (CHOL) adenocarcinoma cohorts within The Cancer Genome Atlas were used for differential methylation analyses. Clinicodemographic predictors of BCAT1, IKZF1and SEPT9methylation, and the selectivity of hypermethylated BCAT1, IKZF1and SEPT9for colorectal adenocarcinomas in comparison to other cancers were each explored with beta regression.ResultsHypermethylated BCAT1, IKZF1and SEPT9were each differentially methylated in colorectal and gastroesophageal adenocarcinomas. IKZF1was differentially methylated in pancreatic adenocarcinoma. Hypermethylated DNA biomarkers BCAT1, IKZF1and SEPT9were largely stable across different stages of disease and were highly selective for gastrointestinal adenocarcinomas relative to other cancer types.DiscussionExisting CRC methylated ctDNA blood tests for BCAT1/IKZF1and SEPT9might be usefully repurposed for use in other gastrointestinal adenocarcinomas and warrant further prospective ctDNA studies.

Published
2024
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29. Progress in the field of noninvasive diagnostics for colorectal cancer: a systematic review for the accuracy of blood-based biomarkers for detection of advanced pre-cancerous lesions.

Author

Goyal, Rishabh, Wassie, Molla M, Winter, Jean M, Lathlean, Timothy JH, Young, Graeme P, and Symonds, Erin L

Abstract

Early detection of pre-cancerous adenomas through screening can reduce colorectal cancer (CRC) incidence. Fecal immunochemical tests are commonly used, but have limited sensitivity for pre-cancerous lesions. Blood-based screening may improve test sensitivity. This systematic review and meta-analysis was conducted to evaluate the accuracy of blood-based biomarkers for detection of advanced pre-cancerous lesions. We present the accuracy of blood-based biomarkers for the detection of advanced pre-cancerous lesions. EMBASE, Web of Science and PubMed databases were searched, with study populations limited to adults diagnosed with advanced pre-cancerous lesions at colonoscopy, who had a blood-based biomarker test analyzed with reports of sensitivity and specificity. 69 studies were identified, which assessed 133 unique biomarkers sets. The best performing test was a panel of 6 miRNAs, with a sensitivity of 95% and specificity of 90% for advanced pre-cancerous lesions. Only 6 biomarkers demonstrated sensitivity ≥ 50% and specificity ≥ 90% for the detection of advanced pre-cancerous lesions. Many different blood-based biomarkers have been assessed for detection of advanced pre-cancerous lesions, but few have progressed beyond the discovery stage. While some biomarkers have reported high sensitivity and specificity, larger prospective studies in unbiased intended-use screening populations are required for validation. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Web-based communication strategies designed to improve intention to minimize risk for colorectal cancer: Randomized controlled trial

Author

Wilson, Carlene, Flight, Ingrid, Zajac, Ian T, Turnbull, Deborah, Young, Graeme P, Olver, Ian, Wilson, Carlene, Flight, Ingrid, Zajac, Ian T, Turnbull, Deborah, Young, Graeme P, and Olver, Ian

Subjects
Cancer Research, medicine.medical_specialty, Information access, Information needs, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Information seeking behavior, medicine, health communication, Relevance (information retrieval), 030212 general & internal medicine, Health communication, Uncategorized, information seeking behavior, Original Paper, Clinical trial, Oncology, 030220 oncology & carcinogenesis, Family medicine, randomized controlled trial, Cohort, consumer health information, internet, Psychology
Abstract

Background: People seek information on the Web for managing their colorectal cancer (CRC) risk but retrieve much personally irrelevant material. Targeting information pertinent to this cohort via a frequently asked question (FAQ) format could improve outcomes. Objective: We identified and prioritized colorectal cancer information for men and women aged 35 to 74 years (study 1) and built a website containing FAQs ordered by age and gender. In study 2, we conducted a randomized controlled trial (RCT) to test whether targeted FAQs were more influential on intention to act on CRC risk than the same information accessed via a generic topic list. Secondary analyses compared preference for information delivery, usability, relevance, and likelihood of recommendation of FAQ and LIST websites. Methods: Study 1 determined the colorectal cancer information needs of Australians (N=600) by sex and age group (35-49, 50-59, 60-74) through a Web-based survey. Free-text responses were categorized as FAQs: the top 5 issues within each of the 6 cohorts were identified. Study 2 (N=240) compared the impact of presentation as targeted FAQ links to information with links presented as a generic list (LIST) and a CONTROL (no information) condition. We also tested preference for presentation of access to information as FAQ or LIST by adding a CHOICE condition (a self-selected choice of FAQs or a list of information topics). Results: Study 1 showed considerable consistency in information priorities among all 6 cohorts with 2 main concerns: treatment of CRC and risk factors. Some differences included a focus on general risk factors, excluding diet and lifestyle, in the younger cohort, and on the existence of a test for CRC in the older cohorts. Study 2 demonstrated that, although respondents preferred information access ordered by FAQs over a list, presentation in this format had limited impact on readiness to act on colorectal cancer risk compared with the list or a no-information control (P=.06). Both FAQ and LIST were evaluated as equally usable. Those aged 35 to 49 years rated the information less relevant to them and others in their age group, and information ordered by FAQs was rated, across all age groups and both sexes, as less relevant to people outside the age group targeted within the FAQs. Conclusions: FAQs are preferred over a list as a strategy for presenting access to information about CRC. They may improve intention to act on risk, although further research is required. Future research should aim to identify better the characteristics of information content and presentation that optimize perceived relevance and fully engage the target audience. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12618000137291; https://www.anzctr.org. au/Trial/Registration/TrialReview.aspx?id=374129 (Archived by WebCite at http://www.webcitation.org/6x2Mr6rPC) [JMIR Cancer 2018;4(1):e2]

Published
2023
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36. Supplementary Methods, Supplementary Figures 1-2, and Supplementary Tables 1-2. from Demand for Colonoscopy in Colorectal Cancer Screening Using a Quantitative Fecal Immunochemical Test and Age/Sex-Specific Thresholds for Test Positivity

Author

Chen, Sam Li-Sheng, primary, Hsu, Chen-Yang, primary, Yen, Amy Ming-Fang, primary, Young, Graeme P., primary, Chiu, Sherry Yueh-Hsia, primary, Fann, Jean Ching-Yuan, primary, Lee, Yi-Chia, primary, Chiu, Han-Mo, primary, Chiou, Shu-Ti, primary, and Chen, Hsiu-Hsi, primary

Published
2023
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38. Recommendations on the Use of Multiple Labels in Human Mass Balance Studies

Author

Cuyckens, Filip, Hvenegaard, Mette G., Cassidy, Kenneth C., Spracklin, Douglas K., James, Alexander D., Pedersen, Mette L., Scarfe, Graeme, Wagner, David S., Georgi, Katrin, Schulz, Simone I., Schieferstein, Hanno, Bjornsdottir, Inga, Romeo, Andrea A., Da Violante, Georges, Blech, Stefan, Moliner, Patricia, and Young, Graeme C.

Abstract

The administration of radiolabeled drug candidates is considered the gold standard in absorption, distribution, metabolism, and excretion studies for small-molecule drugs since it allows facile and accurate quantification of parent drug, metabolites, and total drug-related material independent of the compound structure. The choice of the position of the radiolabel, typically 14C or 3H, is critical to obtain relevant information. Sometimes, a biotransformation reaction may lead to cleavage of a part of the molecule. As a result, only the radiolabeled portion can be followed, and information on the fate of the nonlabeled metabolite may be lost. Synthesis and administration of two or more radiolabeled versions of the parent drug as a mixture or in separate studies may resolve this issue but comes with additional challenges. In this paper, we address the questions that may be considered to help make the right choice whether to use a single or multiple radiolabel approach and discuss the pros and cons of different multiple-labeling strategies that can be taken as well as alternative methods that allow the nonlabeled part of the molecule to be followed.SIGNIFICANCE STATEMENTRadiolabeled studies are the gold standard in drug metabolism research, but molecules can undergo cleavage with loss of the label. This often results in discussions around potential use of multiple labels, which seem to be occurring with increased frequency since an increasing proportion of the small-molecule drugs are tending towards larger molecular weights. This review provides insight and decision criteria in considering a multiple-label approach as well as pros and cons of different strategies that can be followed.

Published
2024
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