Mass spectrometry based protein profiling : taking the steps towards clinical application

  In this thesis mass spectrometry based protein profiling was applied as a new biomarker screening modality and it was evaluated whether or not this could be translated into early detection of breast cancer and pancreatic cancer. The status of breast cancer screening by proteomic profiling is discussed. Which steps have already been made? What is essential to implement this techniques in a clinical setting? Furthermore, the new protein profiling screening methods for pancreatic cancers are evaluated. Future studies will be suggested that are needed to translate this promising biomarker into a clinical application.  Abbie; Fagron; Chipsoft; GaldermaLUMC / Geneeskund

Serum peptide signatures for pancreatic cancer based on mass spectrometry: a comparison to CA19-9 levels and routine imaging techniques

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

On the use of double cross-validation for the combination of proteomic mass spectral data for enhanced diagnosis and prediction

International audienceWe consider a proteomic mass spectrometry case-control study for the calibration of a diagnostic rule for the detection of early-stage breast cancer. For each patient, a pair of two distinct mass spectra is recorded, each of which derived from a different prior fractionation procedure on the available patient serum. We propose a procedure to combine the distinct spectral expressions from patients for the calibration of a diagnostic discriminant rule. This is achieved by first calibrating two distinct prediction rules separately, each of which on only one of the two available spectral data sources. A double cross-validatory approach is used to summarize the available spectral data using the two classifiers to posterior class probabilities, on which a combined predictor can be calibrated

Mass spectrometry based protein profiling : taking the steps towards clinical application

  In this thesis mass spectrometry based protein profiling was applied as a new biomarker screening modality and it was evaluated whether or not this could be translated into early detection of breast cancer and pancreatic cancer. The status of breast cancer screening by proteomic profiling is discussed. Which steps have already been made? What is essential to implement this techniques in a clinical setting? Furthermore, the new protein profiling screening methods for pancreatic cancers are evaluated. Future studies will be suggested that are needed to translate this promising biomarker into a clinical application.  </div

Risicobeoordeling van grondwaterverontreiniging ten gevolge van verlaten opslagplaatsen op landbouwbedrijven in Oekraïne : Afsluitend projectrapport.

Dit is het hoofdrapport. Het bijlagenrapport heeft nummer 680272001-ADit is het hoofdrapport. Het bijlagenrapport heeft rapportnummer 680272001A Oekraïne kampt met een groot aantal puntbronnen van pesticiden en meststoffen die de landbouwgronden en het drinkwater bedreigen. Risicobeoordeling biedt de mogelijkheid om het grote aantal verontreinigde locaties te identificeren en prioriteren als een eerste stap naar sanering van de locaties Toenemende behoeften en afnemende budgetten Centerderzhrodyuchist, het Oekraïense Staatsinstituut voor Bodemvruchtbaarheid en Productkwaliteit, is verantwoordelijk voor zowel de monitoring van bodemkwaliteit als voor bodemvruchtbaarheidanalysen en bemestingsadvies. Het budget voor beide taken neemt af, terwijl de behoefte aan gedetailleerde monitoring en informatieverzameling toeneemt om een voldoende en een veilige voedselproductie voor de toekomst zeker te stellen. Het veiligstellen van landbouwgrond en voedselveiligheid De risico's van grondwaterverontreiniging zijn reëel door uitspoeling van pesticiden en meststoffen uit verlaten en onbeheerde opslagplaatsen voor deze producten in het landelijk gebied. De verontreiniging van het grondwater vormt een bedreiging voor zowel de landbouwproductie (gewasopbrengst en de voedselveiligheid) als voor de drinkwatervoorziening van kleine dorpen. Deze dorpen zijn voor hun drinkwater meestal afhankelijk van locale drinkwaterputten. Prioriteren en differentiëren van puntbronnen Teruglopende budgetten en de hoge kosten gerelateerd aan het saneren van al deze locaties vragen om een methodologie voor risicobeoordeling van puntbronnen. Hieronder wordt verstaan, ten eerste, het uitvoeren van een inventarisatie van relevante puntbronnen en/of processen die de mobiliteit van verontreinigingen beïnvloeden. Ten tweede betekent dit het bepalen in welke mate verontreinigingen in het freatische grondwater terechtkomen en op welke wijze deze worden getransporteerd via grondwaterstroming door de ondergrond. Ten derde houdt het in het uitvoeren van een risicobeoordeling met betrekking tot de land- en watergebruiksfuncties in de nabijheid van puntbronnen. Deze methodologie is uitgewerkt door de Nederlandse en Oekraïense deskundigen en vastgelegd in een leidraad. Financiering en team Bovenstaande bevindingen zijn het resultaat van een project, gefinancierd door Agenschap NL, om de opties te onderzoeken voor het gebruik van aardobservatie en GIS in de bodemkwaliteitsmonitoring in de Oekraïne. Een team van Nederlandse experts, afkomstig van het RIVM, het Planbureau voor de Leefomgeving (PBL) en het adviesbureau Acacia Water BV, heeft dit project in 2011 en 2012 uitgevoerd samen met experts van Centerderzhrodyuchist en experts van twee andere Oekraïense instituten en organisaties, zowel overheid als bedrijfsleven.Ukraine faces large challenges, as point sources of contamination endanger its highly productive, but vulnerable soils and drinking water wells. Risk assessment provides a methodology to prioritize and differentiate the vast amount of potentially contaminated sites in a first step towards remediation. Increasing needs and decreasing budget Centerderzhrodyuchist, the Ukrainian State Centre for Soil Fertility and Product Quality, is responsible for soil quality monitoring in Ukraine as well as soil fertility analysis and advises. The budget for both tasks is decreasing, while the need for detailed monitoring and information collection is increasing to assure sufficient and safe food production in the near future. Safeguarding the agricultural area and food security The risk of groundwater contamination by abandoned on-farm storage sites endangers the agricultural area and drinking water wells. This in turn endangers crop production and as a consequence food security. Prioritizing and differentiate point sources of pollution Decreasing budgets and high costs involved with remediation demand a methodology for risk assessment of point-source contamination. This involves an inventory of relevant point sources and/or contaminant mobilisation processes; secondly, an assessment of the leaching of contaminants into phreatic groundwater and transport in aquifers due to groundwater flow and, thirdly, a risk assessment as regard to land and water use functions in the vicinity of a pointsource of contamination. The Dutch and Ukrainian experts have elaborated this methodology and have laid it down in a guidance document. Sponsor and teams These findings are the result of a project, developed by NL Agency and financed by the Ditch Ministry of Economic Affairs, Agriculture and Innovation, to enable Ukrainian experts to carry out risk assessments for the abandoned on-farm storage sites in Ukraine. A Dutch team, with experts from the National Institute for Public Health and the Environment (RIVM), PBL Netherlands Environmental Assessment Agency and the consultancy firm Acacia Water BV, carried out this project together with experts of Centerderzhrodyuchist and with experts of two other Ukrainian institutes and organisations, both public and private, in 2011 and 2012.NL Agenc

Improved classification of breast cancer peptide and protein profiles by combining two serum workup procedures

PURPOSE Detection of breast cancer at early stage increases patient's survival. Mass spectrometry-based protein analysis of serum samples is a promising approach to obtain biomarker profiles for early detection. A combination of commonly applied solid-phase extraction procedures for clean-up may increase the number of detectable peptides and proteins. In this study, we have evaluated whether the classification performance of breast cancer profiles improves by using two serum workup procedures. METHODS Serum samples from 105 breast cancer patients and 202 healthy volunteers were processed according to a standardized protocol implemented on a high-end liquid-handling robot. Peptide and protein enrichments were carried out using weak-cation exchange (WCX) and reversed-phase (RP) C18 magnetic beads. Profiles were acquired on a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer. In this way, two different biomarker profiles were obtained for each serum sample, yielding a WCX- and RPC18-dataset. RESULTS The profiles were statistically evaluated with double cross-validation. Classification results of WCX- and RPC18-datasets were determined for each set separately and for the combination of both sets. Sensitivity and specificity were 82 and 87 % (WCX) and 73 and 93 % (RPC18) for the individual workup procedures. These values increased up to 84 and 95 %, respectively, upon combining the data. CONCLUSION It was found that MALDI-TOF peptide and protein profiles can be used for classification of breast cancer with high sensitivity and specificity. The classification performance even improved when two workup procedures were applied, since these provide a greater number of features (proteins).Surgical oncolog

EARLY DETECTION OF COLORECTAL CANCER USING MASS SPECTROMETRY BASED SERUM PROTEIN PROFILING

Proteomic