Proteomics: Applications and opportunities in preclinical drug development

Steiner, Sandra; Witzmann, Frank A.

doi:10.1002/1522-2683(20000601)21:11<2099::aid-elps2099>3.0.co;2-n

Cited by 81 publications

(32 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Two-dimensional electrophoresis is the most convenient and straightforward mechanism for identifying such forms, and no other complete separation mechanism or assay exists. Proteomic analysis of rat liver homogenates has been applied to the identification of protein changes corresponding to xenobiotically induced hepatomegaly (22 ) and is particularly useful for the detection of druginduced posttranslational protein modifications after drug-associated liver injury that would not be detectable via mRNA profiling (23 ). Other workers have recently characterized all of the major protein components in serum from healthy CD rats and noted changes in rats treated with hypolipidemic or antiinflammatory drugs (24 ).…”

Section: Discussionmentioning

confidence: 99%

Use of Proteomic Methods to Identify Serum Biomarkers Associated with Rat Liver Toxicity or Hypertrophy

Amacher¹,

Adler²,

Herath

et al. 2005

Clinical Chemistry

View full text Add to dashboard Cite

Background: Our objectives were to identify serum marker proteins in rats that might serve as sensitive indicators of hepatomegaly, hepatocellular necrosis, or hepatobiliary injury and to use them to analyze data from a collaborative proteomics project. Methods: In each of 4 studies comprising the collaborative project, rats were given 1 of 4 compounds that target the liver through different mechanisms. Sera and liver samples were collected by terminal bleeds at 1 of 3 postdose time points. Sera were depleted of major secretory proteins and then separated into protein features by 2-dimensional gel electrophoresis (2DGE). Liver specimens were also processed and subjected to 2DGE. Protein spots that significantly increased or decreased in quantity after drug treatment were recovered, digested, analyzed by mass spectroscopy, and compared with available databases for identification. Criteria for further consideration were (a) temporal expression (i.e., increase or decrease at early, fulminant, or recovery periods), (b) known biological function, (c) probable hepatic origin, and (d) any previous association with toxicity in published studies. Markers that changed significantly at the early time point were important because of their potential sensitivity for signaling minimal damage. Results: Vitamin D-binding protein, paraoxonase, cellular retinol-binding protein, malate dehydrogenase, F-protein, and purine nucleoside phosphorylase were

show abstract

Section: Discussionmentioning

confidence: 99%

Use of Proteomic Methods to Identify Serum Biomarkers Associated with Rat Liver Toxicity or Hypertrophy

Amacher¹,

Adler²,

Herath

et al. 2005

Clinical Chemistry

View full text Add to dashboard Cite

show abstract

“…One such marker is C-reactive protein, an indicator of inflammatory changes in blood vessel walls that presage atherosclerosis. [140][141][142][143][144][145][146][147][148][149][150][151][152][153][154][155][156][157] Microarray technology Nano-biotechnology Nano-biotechnology or nanomedicine is another rapidly moving field. Nanosensors are being developed from particles that are about 50,000 times smaller than the diameter of human hair to detect protein and gene expression in individual cells in the body, thus allowing the assessment of the health of cells at early stages of disease.…”

Section: Antisense Technologymentioning

confidence: 99%

Medical Biotechnology: Problems and Prospects in Bangladesh

Mizan

2013

J Enam Med Col

View full text Add to dashboard Cite

show abstract

“…Proteome profiling is an important research goal, and is being used to identify biomarkers for diagnosis and prognosis of disease, [139][140][141] to compare protein expression levels for clinical monitoring of drug efficacy 142,143 or toxicity 142,144,145 and may someday be useful for personalized medicine. 146 Unfortunately, large-scale protein identification is hampered by the complex, multi-step sample processing regimens that are required prior to analysis.…”

Section: Introductionmentioning

confidence: 99%

A Digital Microfluidic Approach to Proteomic Sample Processing

2009

View full text Add to dashboard Cite

Proteome profiling is the identification and quantitation of all proteins in biological samples. An important application of proteome profiling that has received much attention is clinical proteomics, a field that promises the discovery of biomarkers that will be useful for early diagnosis and prognosis of diseases. While clinical proteomic methods vary widely, a common characteristic is the need for (i) extraction of proteins from complex biological fluids and (ii) extensive biochemical processing (reduction, alkylation and enzymatic digestion) prior to analysis. However, the lack of standardized sample handling and processing in proteomics is a major limitation for the field. The conventional macroscale manual sample handling requires multiple containers and transfers, which often leads to sample loss and contamination. For clinical proteomics to be adopted as a gold standard for clinical measures, the issue of irreproducibility needs to be addressed. A potential solution to this problem is to form integrated systems for sample handling and processing, and in this dissertation, I describe my work towards realizing this goal using digital microfluidics (DMF). DMF is a technique characterized by the manipulation of discrete droplets (100 nL -10 L) on an array of electrodes by the application of electrical fields. It is well-suited for carrying out rapid, sequential, miniaturized automated biochemical assays. This thesis demonstrates how DMF can be a powerful tool capable of automating several protein handling and processing steps used in proteomics.iii Methods for implementing proteomic multi-step solution-phase processes (reduction, alkylation, and digestion) on DMF were developed. This was accompanied by the development of heterogenous enzymatic microreactors for efficient protein digestion. Strategies for reducing non-specific adsorption were developed. Finally, in proof-of-concept work, a combination of protein extraction and protein processing was demonstrated on DMF devices.iv ACKNOWLEDGEMENTS

show abstract

Proteomics: Applications and opportunities in preclinical drug development

Cited by 81 publications

References 58 publications

Use of Proteomic Methods to Identify Serum Biomarkers Associated with Rat Liver Toxicity or Hypertrophy

Use of Proteomic Methods to Identify Serum Biomarkers Associated with Rat Liver Toxicity or Hypertrophy

Medical Biotechnology: Problems and Prospects in Bangladesh

A Digital Microfluidic Approach to Proteomic Sample Processing

Contact Info

Product

Resources

About