Translational Research in Colorectal Cancer

2018 ◽  
Vol 31 (03) ◽  
pp. 145-146
Karin Hardiman
2018 ◽  
Vol 09 (01) ◽  
pp. 054-061 ◽  
C. Maier ◽  
L. Lang ◽  
H. Storf ◽  
P. Vormstein ◽  
R. Bieber ◽  

Background In 2015, the German Federal Ministry of Education and Research initiated a large data integration and data sharing research initiative to improve the reuse of data from patient care and translational research. The Observational Medical Outcomes Partnership (OMOP) common data model and the Observational Health Data Sciences and Informatics (OHDSI) tools could be used as a core element in this initiative for harmonizing the terminologies used as well as facilitating the federation of research analyses across institutions. Objective To realize an OMOP/OHDSI-based pilot implementation within a consortium of eight German university hospitals, evaluate the applicability to support data harmonization and sharing among them, and identify potential enhancement requirements. Methods The vocabularies and terminological mapping required for importing the fact data were prepared, and the process for importing the data from the source files was designed. For eight German university hospitals, a virtual machine preconfigured with the OMOP database and the OHDSI tools as well as the jobs to import the data and conduct the analysis was provided. Last, a federated/distributed query to test the approach was executed. Results While the mapping of ICD-10 German Modification succeeded with a rate of 98.8% of all terms for diagnoses, the procedures could not be mapped and hence an extension to the OMOP standard terminologies had to be made.Overall, the data of 3 million inpatients with approximately 26 million conditions, 21 million procedures, and 23 million observations have been imported.A federated query to identify a cohort of colorectal cancer patients was successfully executed and yielded 16,701 patient cases visualized in a Sunburst plot. Conclusion OMOP/OHDSI is a viable open source solution for data integration in a German research consortium. Once the terminology problems can be solved, researchers can build on an active community for further development.

2017 ◽  
Vol 28 ◽  
pp. vi110 ◽  
I. Rigotto ◽  
M. Schirripa ◽  
D. Costardi ◽  
F. Loupakis ◽  
C. Magro ◽  

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 547-547
Kiran Madanahally Divakar ◽  
Alvin Concepcion ◽  
Jessica Shea ◽  
Smriti Gupta ◽  
Lilly Kong

547 Background: Point mutations in KRAS, NRAS, and BRAF are implicated in the oncogenic RAS/RAF/MEK/ERK pathway and are prognostic and predictive markers in treating metastatic colorectal cancer patients. Here, we report the performance of three single tube highly multiplex and modular KRAS/NRAS/BRAF Assays capable of detecting 30 point mutations from FFPE-extracted DNA on the fully automated Modaplex System. Methods: Primers for multiplex KRAS/NRAS/BRAF Assays to detect 13, 13, and 4 point mutations for KRAS, NRAS, and BRAF genes, respectively, were designed using proprietary technology. Analytical sensitivity of each mutation was assessed using mutation specific ultramer oligos or Horizon Dx Mockblock specimens. Analytical specificity was determined on known wild-type FFPE DNAs. The assays were tested on DNA extracted from clinical FFPE specimens that were characterized by pyrosequencing. Modaplex data on these specimens were compared to pyrosequencing for concordance. Results: The modular Modaplex KRAS/NRAS/BRAF point mutation panels detect and differentiate 30 mutations in the KRAS, NRAS, and BRAF genes in three wells. Each assay requires just 5 µL of clinical sample extract (10-50ng DNA per assay) with a setup time of 15-30 minutes. The total run time including data analysis and setup is 4 hours. The kit includes an internal control to determine mutation status; and calibration controls to determine amplicon size. Analytical studies demonstrate the assays are sensitive (number of copies detected in one reaction), selective (mutant to wild-type ratio), and specific (relative to wild-type genomic DNA background). Nearly 110 clinical FFPE samples were tested, and the assays showed more than 95% concordance with pyrosequencing method (98% for BRAF, 97% for KRAS, and 100% for NRAS). Conclusions: Modaplex KRAS/NRAS/BRAF assays provide an accurate and sensitive method of mutation detection. These automated multiplexed assays to detect key mutations in three genes can be performed on a single platform facilitating clinical or translational research. *Modaplex KRAS/NRAS/BRAF Assays are for Research Use Only. Not for clinical diagnostic use.

2020 ◽  
Vol 21 (11) ◽  
pp. 4105
Alessandro Passardi ◽  
Emanuela Scarpi ◽  
Paola Ulivi

Colorectal cancer (CRC) is the third most frequently diagnosed cancer in the world [...]

2020 ◽  
Vol 10 (3) ◽  
pp. 79 ◽  
Apostolos Papachristos ◽  
Gregory B. Sivolapenko

Bevacizumab is a monoclonal antibody that targets VEGF-A and inhibits tumor angiogenesis. Bevacizumab is approved for the treatment of various cancer, including metastatic colorectal cancer (mCRC), ovarian cancer, lung cancer, and others. Thus, it is widely used in oncology, but contrary to other therapeutic classes, there is still a lack of validating predictive factors for treatment outcomes with these agents. In recent years, the research for factors predictive of anti-VEGF treatments and especially bevacizumab response has been one of the most competitive translational research fields. Herein, we review and present the available literature of the clinical use of biomarkers, pharmacogenomics (PG), and therapeutic drug monitoring (TDM) approaches that can be used for the optimization of bevacizumab use in the era of precision medicine.

Mariska Bierkens ◽  
Wim van der Linden ◽  
Ward Weistra ◽  
Kees van Bochove ◽  
Jeroen A.M. Beliën ◽  

Yue Wang Webster ◽  
Ernst R Dow ◽  
Mathew J Palakal

Even though numerous tools and technologies have been developed to meet this need with various degrees of success, a conceptual framework is needed to fully realize the value of those tools and technologies. The authors propose Complex System (CS) to be the logical foundation of such a framework. Since translational research is a spiral and dynamic process. With the CS mindset, they designed a multi-layer architecture called HyGen (Hypotheses Generation Framework) to address the challenges faced by translational researchers. In order to evaluate the framework, the authors carried out heuristic and quantitative tests in Colorectal Cancer disease area. The results demonstrate the potential of this hybrid approach to bridge silos and to identify hidden links among clinical observations, drugs, genes and diseases, which may eventually lead to the discovery of novel disease targets, biomarkers and therapies.

2018 ◽  
Vol 31 (03) ◽  
pp. 161-167
Molly Ford

AbstractGrowing knowledge of inherited colorectal cancer syndromes has led to better surveillance and better care of this subset of patients. The most well-known entities, including Lynch syndrome and familial adenomatous polyposis, are continually being studied and with the advent of more sophisticated genetic testing, additional genetic discoveries have been made in the field of inherited cancer. This article will summarize many of the updates to both the familiar and perhaps less familiar syndromes that can lead to inherited or early-onset colorectal cancer.

2013 ◽  
Vol 04 (06) ◽  
pp. 44-50 ◽  
Karen-Lise Garm Spindler ◽  
Niels Pallisgaard ◽  
Rikke Fredslund Andersen ◽  
John Ploen ◽  
Anders Jakobsen

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