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Biomarkers - Articles and news items
Molecular diagnostics and biomarker discovery are gaining increasing attraction in clinical research. This includes all fields of diagnostics, such as risk assessment, disease prognosis, treatment prediction and drug application success control. The detection of molecular clinical biomarkers is very widespread and can be developed on various molecular levels, like the genome, the epi-genome, the transcriptome, the proteome or the metabolome. Today, numerous high-throughput laboratory methods allow rapid and holistic screening for such marker candidates. Regardless of which molecular level is analysed, in order to detect biomarker candidates, high sample quality and a standardised and highly reproducible quantification workflow are prerequisites. This article describes an optimal and approved development strategy to discover and validate ‘transcriptional biomarkers’ in clinical diagnostics, which are in compliance with the recently developed MIQE guidelines. We focus on the importance of sample quality, RNA integrity, available screening and quantification methods, and biostatistical tools for data interpretation…
Industry news / 3 February 2015 / AYOXXA Biosystems / SERI
AYOXXA and SERI will work together on validating the company’s multiplexing technology platform for protein biomarker detection, as part of an expanded collaboration for developing ophthalmic diagnostic tools…
Issue 6 2014 / 23 December 2014 / Axel Ducret, Biochemist
This article will focus on some of the critical aspects of transition biomarkers discovered in classical (MS-based) proteomics workflows and on the challenges to be met before validated assays can become more routine in the clinical laboratory…
Issue 6 2014 / 23 December 2014 / The Society for Laboratory Automation & Screening (SLAS)
The Society for Laboratory Automation and Screening (SLAS) is proud to present SLAS2015, the Fourth Annual Conference and Exhibition of the Society…
There is an urgent need to predict which treatment will report the most benefit to a patient with cancer. To that end, scientists are exploring any possible biomolecule in the organism that can mark each individual for its adequate treatment. If achieved, it will open a personalised medicine era.
In recent years, mass spectrometry (MS) based proteomics has moved from being a qualitative tool (used to mainly identify proteins) to a more reliable analysis tool, allowing relative quantitation as well as absolute quantitation of a large number of proteins. However, the developed quantitative methods are either specific for certain types of samples or certain types of mass spectrometers. In some cases, developing expertise on how to use a given method may take a long time and the use of these methods is therefore limited to few laboratories. Other quantitative methods are suitable for simple standard protein mixes which are far from the complexity of real samples. As a consequence, the number of available quantitative methods is high and choosing the right one is challenging.
RNA levels can be measured with very high specificity, sensitivity and accuracy with techniques such as real-time quantitative PCR (qPCR), microarray analysis and next generation sequencing. This makes messenger (m) RNAs and potentially microRNAs and other non-coding RNAs popular as biomarkers. But RNA is less stable and more dynamic than DNA, and assays are not always specific for RNA, so can we trust measured expression values?
A biomarker is a biological molecule found in blood, other body fluids or tissues, and is a sign of a normal or abnormal process, or of a condition or disease1. The biomarker may be used to see how well the body responds to a treatment for a disease or condition. Most popular and common molecular biomarkers are DNA, RNA and proteins. While proteins and in particular DNA are quite stable molecules and can be analysed for many properties such as sequence years after being removed from their natural biological environment, RNA molecules are not (Table 1). The extra 2’-hydroxyl group on the ribose in RNA that is absent in DNA is a nucleophile. It confers catalytic activity to ribozymes, but also makes RNA intrinsically unstable. In aqueous solution, RNA spontaneously degrades through self-cleavage catalysed by metal ions such as Mg2+, high (>9) or low (<2) pH, and temperature. EDTA or citrate is therefore typically added to RNA preserving solutions to chelate Mg2+2. Although RNA is more resistant to ultraviolet (UV) irradiation than DNA, it causes several types of damage including photochemical modification, cross - linking and oxidation.
Biomarkers are biological characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention. Biomarkers can be used to determine disease onset, progression, efficacy of drug treatment, patient susceptibility to develop a certain type of disease or predict efficacy of treatment at a particular disease stage. Protein molecular biomarkers are particularly popular due to the availability of a large range of analytical instrumentation, which can identify and quantify proteins in complex biological samples. Proteins are key compounds in biosynthesis, cell, tissue and organ signalling and provide cell and tissue structural stability in living organisms. The primary protein sequences are encoded in the genome; however, their complex posttranslational modifications (PTMs) and three dimensional structures are fairly unpredictable from genomic information. In this mini-review, we will provide an overview of the current state, challenge and important aspects of protein biomarker discovery and validation…
Issue 3 2012, Proteomics / 10 July 2012 / Paul C. Guest, Department of Chemical Engineering and Biotechnology, University of Cambridge and Sabine Bahn Department of Chemical Engineering and Biotechnology, University of Cambridge & Department of Neuroscience, Erasmus Medical Centre
Pharmaceutical companies are under increasing pressure to improve their efficiency and returns on drug discovery projects. This is a daunting task considering that the average drug costs approximately one billion US dollars to develop and takes around 12 years from initial discovery to reach the market1. In addition, approximately 70 per cent of drugs fail to recover their research and development costs and around 90 per cent fail to provide a satisfactory return on investment. Therefore, minimising risk is one of the most important aims in pharmaceutical discovery programs today.
There are now efforts to establish standard operating procedures to navigate through these problems and, at the same time, meet the regulatory demands. To facilitate this process, the regulatory health authorities have encour aged the incorporation of biomarkers into the drug discovery pipeline and the Food and Drug Administration (FDA) has called for efforts to modernise and standardise approaches for the delivery of more effective and safer drugs2.
Proteomics is the most applicable tech – nology for implementing biomarker app – roaches in drug discovery given that virtually all existing drug targets are proteins3. Proteomics is a systems approach for the global study of protein expression changes4.
Dr Nicholls has over 30 years’ experience of building international businesses…
Cancer Biology, Issue 1 2012 / 28 February 2012 / Janina Staub and Jochen Utikal, Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, University of Heidelberg & Skin Cancer Unit, German Cancer Research Center
During the last few years, significant improvements in the treatment of metastatic melanoma were reported, targeting molecules involved in the pathogenesis of melanoma. Different clinical trials were able to prove a prolonged overall survival by introducing new therapeutic agents. Hereby an imunomodulating therapy with the anti-CTLA-4 antibody ipilimumab has been established. Other promising treatment possibilities include targeted therapies for melanoma patients showing certain activating mutations in their tumour cells, e.g. BRAF V600 mutations and their selective inhibition by vemurafenib or the inhibition of the c-Kit receptor by drugs such as imatinib mesylate. This review will provide a brief overview of the latest therapeutic strategies and recent achievements in treating metastatic melanoma, as well as discuss the arising problems with resistance mechanisms to selective therapies. It will also highlight future approaches to combine specific treatments in an attempt to individualise melanoma treatment for every patient with the best possible efficacy and outcome…
Whitepapers / 1 February 2012 / Oxford Gene Technology
Download this free white paper for detailed insight into the advantages of autoantibodies as biomarkers, including a review of the current technology and best practices for identification of sensitive and specific autoantibody biomarkers.
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