Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “differential proteomics analysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,441 records · Page 80Linked to original sources
PubMed2004

Effects of benzo(a)pyrene on protein expression in Jurkat T-cells.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants of air, water and soil, and are produced by the incomplete combustion of organic materials. The International Agency for Research on Cancer has characterized PAHs as carcinogens. In this study, we investigated the effects of benzo(a)pyrene (B(a)P), which is the most carcinogenic member of the PAHs, on Jurkat cell protein by proteomic analysis. Jurkat cells were treated with various concentrations of B(a)P (0, 2.5, 5, 10, 20 or 40 microM) for 24 or 48 h and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and lactate dehydrogenase assays were carried out to determine cytotoxicity and a Comet assay was used to determinate genotoxicity. The cytotoxicity assays showed that 2.5 microM of B(a)P was the maximal concentration that did not cause any toxicity, but nevertheless, at this level B(a)P produced significant DNA damage in Jurkat cells at 48 h. Proteomic analysis using three different pI ranges and large two-dimensional gel electrophoresis showed 3427 protein spots. A total of 46 (13 up- and 33 down-regulated) proteins were identified as biomarkers of B(a)P and showed dose-dependent expressions in Jurkat T-cell line exposed to B(a)P. Of these, 27 protein spots were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Two functionally differentiated protein groups were found. The protein group involving apoptosis and tumor suppression were found to be up-regulated, and B(a)P down-regulated enzyme was involved in energy metabolism, DNA synthesis and in cell structure and motility.

Benzo(a)pyrene↗
PubMed2025

Diagnosing the undiagnosed: AI-enhanced multimodal modeling for placental mesenchymal dysplasia in high-risk pregnancies.

Placental mesenchymal dysplasia (PMD) is a rare vascular placental disorder that mimics molar pregnancy but often coexists with a viable fetus, making its misdiagnosis potentially devastating. In high-risk pregnancies, artificial intelligence (AI)-enhanced multimodal modeling - incorporating imaging, genomics, proteomics, and clinical features - offers a transformative diagnostic strategy. Leveraging Bayesian hyperparameter optimization for model refinement, this approach improves diagnostic accuracy while reducing uncertainty and clinician hesitation. Recent clinical studies support its efficacy and interpretability through SHAP and LIME models, while real-time surgical enhancements using Bayesian methods highlight its broader clinical utility. Despite current challenges such as data heterogeneity and integration barriers, multimodal AI provides unprecedented resolution in placental analysis, enabling precise differentiation between PMD and similar fetopathies. Ultimately, this advancement supports timely, non-invasive diagnosis, personalized management, and emotionally informed decision-making aligned with ethical AI implementation standards.

Bayesian optimization↗
PubMed2005

Calcium influences cellular and extracellular product formation during biofilm-associated growth of a marine Pseudoalteromonas sp.

Bacteria undergo a variety of physiological changes following a switch from planktonic growth to surface-associated biofilm growth. Here, it is shown that biofilm development of a marine isolate, Pseudoalteromonas sp. 1398, results in global changes in its cytosolic and extracellular proteomes. Calcium influences these proteome responses, and affects the amount of surface-associated biomass and extracellular matrix material produced by Pseudoalteromonas sp. 1398. Four extracellular proteins, characterized by N-terminal sequencing, showed increased abundances, while one protein, flagellin, showed reduced abundance at higher [Ca(2+)]. Immunoblotting and transmission-electron-microscopy analysis confirmed that higher [Ca(2+)] and surface-associated growth results in the repression of flagella production. Two-dimensional gel electrophoresis (2DGE) studies combined with cluster analysis of global proteome responses demonstrated that Ca(2+) had a greater regulatory influence on Pseudoalteromonas sp. growing in biofilms than on planktonic cultures. Approximately 22 % of the total cytosolic proteins resolved by 2DGE had differing abundances in response to a switch from planktonic growth to surface-associated growth when the cells were cultivated in 1 mM Ca(2+). At higher [Ca(2+)] this number increased to 38 %. Fifteen cellular proteins that were differentially expressed in response to biofilm growth and/or Ca(2+) were analysed by N-terminal sequencing and/or MS/MS. These proteins were identified as factors involved in cellular metabolic functions, putative proteases and transport proteins, although there were several proteins that had not been previously characterized. These results indicate that Ca(2+) causes global changes in matrix material, as well as in cellular and extracellular protein profiles of Pseudoalteromonas sp. 1398. These changes are more pronounced when the bacterium grows in biofilms than when it grows in planktonic culture.

Bacterial Proteins↗
PubMed2003

Model building and model checking for biochemical processes.

A central claim of computational systems biology is that, by drawing on mathematical approaches developed in the context of dynamic systems, kinetic analysis, computational theory and logic, it is possible to create powerful simulation, analysis, and reasoning tools for working biologists to decipher existing data, devise new experiments, and ultimately to understand functional properties of genomes, proteomes, cells, organs, and organisms. In this article, a novel computational tool is described that achieves many of the goals of this new discipline. The novelty of this system involves an automaton-based semantics of the temporal evolution of complex biochemical reactions starting from the representation given as a set of differential equations. The related tools also provide ability to qualitatively reason about the systems using a propositional temporal logic that can express an ordered sequence of events succinctly and unambiguously. The implementation of mathematical and computational models in the Simpathica and XSSYS systems is described briefly. Several example applications of these systems to cellular and biochemical processes are presented: the two most prominent are Leibler et al.'s repressilator (an artificial synthesized oscillatory network), and Curto- Voit-Sorribas-Cascante's purine metabolism reaction model.

Biochemical Phenomena↗
PubMed2006

Pituitary tumours: findings from whole genome analyses.

Pituitary tumours are common intracranial neoplasms that cause significant morbidity through mass effects and/or the inappropriate secretion of pituitary hormones. Despite a considerable literature detailing potential pathogenic changes in these tumours, their aetiology remains largely unresolved. Recent studies have employed genome-wide profiling towards the identification of novel genes and pathways that are inappropriately expressed or regulated in this tumour type. The techniques employed vary in their complexity and interpretation; however, many of the findings from these types of studies have identified novel genes with potential and, in some cases, proven roles in pituitary tumorigenesis. These studies include comparative genomic hybridization, whole genome-wide allelotyping and methodologies for identification of novel genes associated with epigenetic silencing. In addition, differential display methodologies have been instrumental in the identification of transcripts inappropriately expressed including, pituitary tumour transforming gene, growth arrest and DNA damage-inducible protein (GADD)45gamma and a maternal expressed gene 3 isoform, which in some cases have proven roles in pituitary tumorigenesis. Although few studies of whole genome transcript analysis, as determined by microarray or gene-chip technologies, are reported, these studies of human pituitary, in some cases combined with proteomics, are yielding useful data. In addition, these types of investigation have been applied to several animal models of pituitary tumorigenesis, and in these cases novel genes are highlighted as showing significant change. The identification of the initiating events responsible for the transformation of a normal pituitary cell into one with unrestrained proliferative capacity has so far eluded us. No doubt, these new technologies allowing an essentially unbiased genome-wide analysis, perhaps in combination with animal models that display a preceding hyperplasia, will allow us to identify genes critical to tumour evolution and progression.

DNA Damage↗
PubMed2006

Analysis of outer membrane proteome of Escherichia coli related to resistance to ampicillin and tetracycline.

The elucidation of the molecular details of antibiotic resistance will lead to improvements in extending the efficacy of current antimicrobials. In the current study, proteomic methodologies were applied to characterize functional outer membrane proteins (Omps) of E. coli K-12 responded to tetracycline and ampicillin resistance for understanding of universal pathways that form barriers for antimicrobial agents. For this purpose, E. coli K-12 expressional outer membrane proteome was characterized and identified with the use of 2-DE and MALDI-TOF/MS methods. Then, differential Omps due to tetracycline or ampcilin resistance were determined by comparison between tetracycline minimum inhibitory concentration (MIC)10, ampicillin MIC10, control0 and control10, showing 9 proteins with 11 spots for tetracycline and 8 protein with 9 spots for ampicillin, showing a difference in only 1 protein (decreased LamB in tetracyclin) between the two antibiotics. Among the proteins, 3 were known as antibiotic-resistant proteins, including TolC, OmpC and YhiU, while FimD precursor, LamB, Tsx, YfiO, OmpW, NlpB were first reported here to be antibiotic-resistance-related proteins. Our findings will be helpful for further understanding of antibiotic-resistant mechanism(s). This study also shows that the combination of Omp purification methods certainly contributes the sensitivity of Omp detection.

Ampicillin↗
PubMed2026

Plasma Proteomics Identifies Thousand-and-One-Amino Acid Kinase 3 as a Potential Biomarker of Rheumatoid Arthritis Activity and a Novel Therapeutic Target.

OBJECTIVE: Bone destruction associated with active rheumatoid arthritis (RA) remains a major therapeutic challenge, with a lack of reliable molecular markers reflecting bone injury. This study aims to identify novel biomarkers linked to bone destruction in active RA through proteomic analysis, providing new strategies for precise monitoring and targeted therapy. METHODS: Data-independent acquisition mass spectrometry was used for proteomic quantification and bioinformatic analysis on plasma samples from 160 patients with RA and 40 healthy controls. Key proteins associated with bone destruction were screened by integrating Sharp scores with synovial single-cell RNA sequencing data and subsequently validated in two independent cohorts (N1 = 50 and N2 = 10) using enzyme-linked immunosorbent assay and multiplex immunohistochemistry. Functional studies were conducted using fibroblast-like synoviocytes (FLSs) in vitro and a collagen-induced arthritis (CIA) mouse model in vivo. RESULTS: A total of 4,998 plasma proteins were identified, with 506 showing significant differential expression between active and remitted RA. Thousand-and-one-amino acid kinase 3 (TAOK3) levels were positively associated with Sharp scores and markedly elevated in patients with active RA. Combining TAOK3 with C-reactive protein improved diagnostic accuracy for active RA (area under the curve = 0.915). High TAOK3 expression was also associated with increased relapse frequency. Functional studies showed that TAOK3 knockdown suppressed the tumor-like phenotype of FLSs and down-regulated matrix metalloproteinase 1/2/3 and cathepsin K, whereas TAOK3 overexpression promoted pannus cell-mediated bone erosion, mitigated by TAOK3-targeted inhibitor. In vivo, its inhibition showed therapeutic effects in CIA mice. CONCLUSION: TAOK3 serves as a potential biomarker for bone destruction in active RA and as a therapeutic target for precision monitoring and intervention.

Arthritis, Rheumatoid↗
PubMed2002

Protein-based analysis of alternative splicing in the human genome.

Understanding the functional significance of alternative splicing and other mechanisms that generate RNA transcript diversity is an important challenge facing modern-day molecular biology. Using homology-based, protein sequence analysis methods, it should be possible to investigate how transcript diversity impacts protein structure and function. To test this, a data mining technique ("DiffHit") was developed to identify and catalog genes producing protein isoforms which exhibit distinct profiles of conserved protein motifs. We found that out of a test set of over 1,300 alternatively spliced genes with solved genomic structure, over 30% exhibited a differential profile of conserved InterPro and/or Blocks protein motifs across distinct isoforms. These results suggest that motif databases such as Blocks and InterPro are potentially useful tools for investigating how alternative transcript structure affects gene function.

Algorithms↗
PubMed2002

Acute and chronic effect of dietary phosphorus restriction on protein expression in young rat renal proximal tubules.

Renal proximal tubules play a vital role in phosphorus (P) homeostasis. It is well known that dietary P restriction up-regulates the activities of 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1-OHase), an enzyme that is involved in activation of vitamin D and thereby maintaining P balance. However, the mechanism involved in such regulation is not known. In the present study, we aim to identify proteins that might be involved in the renal adaptation to dietary P restriction using a proteomic approach. Renal proximal tubules were harvested from young rats fed either normal P diet or low P diet (LPD) for 1 to 7 days. Western blotting analysis of 1-OHase and signaling proteins in insulin-like growth factor I axis indicated an increase in expression of these proteins upon dietary P restriction. Using two-dimensional electrophoresis, we found that LPD reduced the total number of protein species expressed in renal proximal tubules. Differentially expressed proteins were analyzed and located using the software Melanie III, and their identities were found using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Our results showed that beta-actin, gamma-actin, major urinary protein, phosphatidylinositol transfer protein beta isoform, and G1/S-specific cyclin D3 are up-regulated and nonspecific lipid transfer protein is down-regulated by LPD.

Actins↗
PubMed2005

Genetic expression profiles and biologic pathway alterations in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is associated with considerable mortality and morbidity and is a major public health concern worldwide. To date, > 20 studies incorporating DNA microarray analyses have examined genomewide genetic expression changes associated with the development of HNSCC. The authors identified published reports of genetic expression profiles of HNSCC by Medline database search. They performed a review of the reports to identify genes that have been found repeatedly to exhibit substantially altered expression in HNSCC. Genes with altered expression were subsequently examined in the context of defined biologic systems with the use of GenMapp 2.0 pathway analysis software. Genes most commonly found to exhibit altered expression were those encoding for cytoskeletal and extracellular matrix proteins, inflammatory mediators, proteins involved in epidermal differentiation, and cell adhesion molecules. Results of GenMapp 2.0 analysis suggested global down-regulation of genes that encode for ribosomal proteins and enzymes in the cholesterol biosynthesis pathway; and up-regulation of genes that encode for matrix metalloproteinases and genes that bear on the inflammatory response. The review indicated that there are several genes and pathways that exhibit substantially altered expression in cancerous versus noncancerous states across studies. Further investigation into the genomic, proteomic, and functional consequences of these gene expression alterations may provide insight into the pathophysiology of HNSCC.

Carcinoma, Squamous Cell↗
PubMed2026

ProtPen Combines Sequence- and Structure-based Approaches to Facilitate Protein Function Predictions on a Proteome-wide Scale.

Proteins of unknown function represent a significant gap in our understanding of biological processes, encompassing large portions of the proteomes of many organisms, especially prokaryotes. Addressing this gap is critical to understanding the biology and pathogenicity of such organisms. We introduce ProtPen, an open-source pipeline that facilitates protein function prediction by combining eggNOG-mapper for sequence-based annotation with Foldseek for rapid structural similarity searches using AlphaFold-predicted protein structures. Annotation results from both tools are merged and enriched with UniProt metadata to produce a comprehensive output suitable for downstream analysis. The pipeline requires only a FASTA input file with UniProt identifiers, and is designed to analyze data sets on the scale of whole proteomes. Benchmarking on a curated data set of well-characterized Pseudomonas aeruginosa proteins demonstrated an annotation accuracy of >90%, and highlighted the complementarity of sequence- and structure-based methods. Further evaluation of ProtPen included its application to biologically relevant data sets, comprising proteins of unknown function that exhibited significant differential abundances in a proteomics data set of P. aeruginosa, and uncharacterized glycoproteins from Haloferax volcanii. ProtPen is readily extensible to incorporate additional protein function prediction tools. In summary, this pipeline facilitates the systemwide annotation of proteins of unknown function from proteomic data sets and whole proteomes.

Pseudomonas aeruginosa↗
PubMed2005

Identification of the hydrophobic glycoproteins of Caenorhabditis elegans.

Hydrophobic proteins such as integral membrane proteins are difficult to separate, and therefore to study, at a proteomics level. However, the Asn-linked (N-linked) carbohydrates (N-glycans) contained in membrane glycoproteins are important in differentiation, embryogenesis, inflammation, cancer and metastasis, and other vital cellular processes. Thus, the identification of these proteins and their sites of glycosylation in a well-characterized model organism is the first step toward understanding the mechanisms by which N-glycans and their associated proteins function in vivo. In this report, a proteomics method recently developed by our group was applied to identify 117 hydrophobic N-glycosylated proteins of Caenorhabditis elegans extracts by analysis of 195 glycopeptides containing 199 Asn-linked oligosaccharides. Most of the proteins identified are involved in cell adhesion, metabolism, or the transport of small molecules. In addition, there are 18 proteins for which no function is known or predictable by sequence homologies and two proteins which were previously predicted to exist only on the basis of genomic sequences in the C. elegans database. Because N-glycosylation is initiated in the lumen of the endoplasmic reticulum (ER), our data can be used to reassess the previously predicted subcellular localizations of these proteins. As well, the identification of N-glycosylation sites helps establish the membrane topology of the associated glycoproteins. Caenorhabditis elegans strains are presently available with mutations in 17 of the genes we have identified. The powerful genetic tools available for C. elegans can be used to make other strains with mutations in genes encoding N-glycosylated proteins and thereby determine N-glycan function.

Animals↗
PubMed2006

Comparative proteomics of cerebrospinal fluid in neuropathologically-confirmed Alzheimer's disease and non-demented elderly subjects.

OBJECTIVES: Diagnostic tests able to reveal Alzheimer's disease (AD) in living patients before cognitive ability is destroyed are urgently needed. Such tests must distinguish AD from other dementia causes, as well as differentiate subtle changes associated with normal aging from true pathology emergence. A single biomarker offering such diagnostic and prognostic capacities has eluded identification. Therefore, a valuable test for AD is likely to be based on a specific pattern of change in a set of proteins, rather than a single protein. METHODS: We examined pooled cerebrospinal fluid (CSF) samples obtained from neuropathologically-confirmed AD (n=43) and non-demented control subjects (n=43) using 2-dimensional gel electrophoresis (2DE) proteomic methodology to detect differentially expressed proteins. Proteins exhibiting expression level differences between the pools were recovered and identified using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. RESULTS: Five differentially-expressed proteins with potential roles in amyloid-beta metabolism and vascular and brain physiology [apolipoprotein A-1 (Apo A-1), cathepsin D (CatD), hemopexin (HPX), transthyretin (TTR), and two pigment epithelium-derived factor (PEDF) isoforms] were identified. Apo A-1, CatD and TTR were significantly reduced in the AD pool sample, while HPX and the PEDF isoforms were increased in AD CSF. DISCUSSION: These results suggest that multi-factor proteomic pattern analysis of the CSF may provide a means to diagnose and assess AD.

Aged↗
PubMed2005

Molecular circuits of resolution: formation and actions of resolvins and protectins.

The cellular events underlying the resolution of acute inflammation are not known in molecular terms. To identify anti-inflammatory and proresolving circuits, we investigated the temporal and differential changes in self-resolving murine exudates using mass spectrometry-based proteomics and lipidomics. Key resolution components were defined as resolution indices including Psi(max), the maximal neutrophil numbers that are present during the inflammatory response; T(max), the time when Psi(max) occurs; and the resolution interval (R(i)) from T(max) to T(50) when neutrophil numbers reach half Psi(max). The onset of resolution was at approximately 12 h with proteomic analysis showing both haptoglobin and S100A9 levels were maximal and other exudate proteins were dynamically regulated. Eicosanoids and polyunsaturated fatty acids first appeared within 4 h. Interestingly, the docosahexaenoic acid-derived anti-inflammatory lipid mediator 10,17S-docosatriene was generated during the R(i). Administration of aspirin-triggered lipoxin A(4) analog, resolvin E1, or 10,17S-docosatriene each either activated and/or accelerated resolution. For example, aspirin-triggered lipoxin A(4) analog reduced Psi(max), resolvin E1 decreased both Psi(max) and T(max), whereas 10,17S-docosatriene reduced Psi(max), T(max), and shortened R(i). Also, aspirin-triggered lipoxin A(4) analog markedly inhibited proinflammatory cytokines and chemokines at 4 h (20-50% inhibition), whereas resolvin E1 and 10,17S-docosatriene's inhibitory actions were maximal at 12 h (30-80% inhibition). Moreover, aspirin-triggered lipoxin A(4) analog evoked release of the antiphlogistic cytokine TGF-beta. These results characterize the first molecular resolution circuits and their major components activated by specific novel lipid mediators (i.e., resolvin E1 and 10,17S-docosatriene) to promote resolution.

Animals↗
PubMed2003

Comprehensive expression profiling by muscle tissue class and identification of the molecular niche of extraocular muscle.

Muscle tissue is an elegant model for biologic integration of structure with function and is frequently affected by a variety of inherited diseases. Traditional muscle classes--skeletal, cardiac, and smooth--share basic aspects of contractile and energetics mechanisms but also have distinctive role-specific adaptations. We used large-scale oligonucleotide microarrays to broaden knowledge of the adaptive expression patterns underlying muscle tissue differences and to identify transcript subsets that are most likely to represent candidate disease genes. Using stringent analysis criteria, we found >or=95 transcripts, which were preferentially expressed by each muscle class and were validated by inclusion of known muscle class-specific and inherited disease-related genes. Differentially expressed transcripts not previously identified as class-specific extend understanding of muscle class transcriptomes and may represent novel muscle-specific disease genes. We also analyzed the expression profile of extraocular muscle, which is divergent from other skeletal muscles, in the broader context of all major muscle classes. Data show that the extraocular muscle phenotype results from the combination of tissue-specific transcripts, novel expression levels of skeletal muscle transcripts, and partial sharing of gene expression patterns with cardiac and smooth muscle. These, and additional proteomic data, establish that extraocular muscle does not constitute a distinctive muscle class but that it does occupy a novel niche within the skeletal muscle class.

Animals↗
PubMed2005

Multiplex multidimensional nanoLC-MS system for targeted proteomic analyses.

The present work describes a dual-column and dual-sprayer LC-MS system for high-throughput proteomic analyses. This system consists of two precolumns for sample desalting and two analytical columns. Each column is terminated by a nanoelectrospray emitter mounted on a robotic arm enabling their sequential positioning in front of the sampling cone of the mass spectrometer. The effluent from each emitter is recorded in separate acquisition channels without detectable crosstalk. Gradient elution to both nanoLC columns is delivered by a single HPLC system via a flow splitter. The reproducibility of retention time and peak intensity of the present multiplex system were comparable to those obtainable using a single emitter configuration. Replicate injections of complex tryptic digests (n = 10) indicated that this system provided good reproducibility of retention time and peak intensity on both columns with RSD values of less than 0.9 and 18.6%, respectively. The application of this system is demonstrated for the monitoring of protein expression changes in U937 human monocyte cells with and without phorbol ester administration. Furthermore, we also demonstrated the use of this multiplex system in a 2-D LC configuration to increase sample loading and throughput for the analysis of biomarker samples of higher complexity. Variations in peptide abundance down to two-fold change were identified across salt fractions for spiked tryptic digests present at a level of 50 fmol in 1.5 microg of plasma samples.

Animals↗
PubMed2005

Proteomics of breast cancer: enhanced expression of cytokeratin19 in human epidermal growth factor receptor type 2 positive breast tumors.

The human epidermal growth factor receptor, type 2 (HER-2/neu or c-erbB-2) is a 185 kDa transmembrane protein that is phosphorylated upon ligand binding and dimerization with members of the HER/c-erbB family and regulates cell growth and differentiation. Its overexpression is strongly associated with advanced disease, metastasis and poor clinical outcome. To better understand the mechanisms underlying the poor prognosis of breast tumors with HER-2/neu-positive status, parallel proteomic analyses were performed on estrogen receptor-negative and node-positive breast tumors with or without overexpression of the HER-2/neu oncogene, using laser capture microdissection and two-dimensional gel electrophoresis. The differentially expressed proteins were identified by peptide mass fingerprinting using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Cytokeratin 19 (CK19), one of the identified proteins, was highly expressed in the HER-2/neu-positive breast tumors when compared with HER-2/neu-negative breast tumors. The enhanced overexpression of CK19 in HER-2/neu-positive tumors was further analyzed using semiquantitative reverse-transcription polymerase chain reaction, Western blotting and reverse-phase protein arrays. Immunohistochemical staining of sections from a breast tumor tissue microarray of 97 tumors showed moderate to strong staining against anti-CK19 antibody in 20 (5 with moderate and 15 with strong staining) of the 26 HER-2/neu-positive tumors (76.9%) and in 22 (12 with moderate and 10 with strong staining) of 52 HER-2/neu-negative tumors (48%) (p = 0.002). Our results indicate that CK19, an intermediate fragment of the cytoskeleton, and other proteins showing differential expression, are likely to be intricately involved in intra- and intercellular molecular events driving the more aggressive tumor proliferation, invasion and metastasis associated with HER-2/neu-positive tumors.

Breast Neoplasms↗
PubMed2004

The application of proteomics to the human alcoholic brain.

Alcoholism results in changes in the human brain that reinforce the cycle of craving and dependency, and these changes are manifest in the pattern of expression of proteins in key cells and brain areas. Described here is a proteomics-based approach aimed at determining the identity of proteins in the superior frontal cortex (SFC) of the human brain that show different levels of expression in autopsy samples taken from healthy and long-term alcohol abuse subjects. Soluble protein fractions constituting pooled samples combined from SFC biopsies of four well-characterized chronic alcoholics (mean consumption > 80 g ethanol/day throughout adulthood) and four matched controls (<20 g/day) were generated. Two-dimensional electrophoresis was performed in triplicate on alcoholic and control samples and the resultant protein profiles analyzed for differential expression. Overall, 182 proteins differed by the criterion of twofold or more between case and control samples. Of these, 139 showed significantly lower expression in alcoholics, 35 showed significantly higher expression, and 8 were new or had disappeared. To date, 63 proteins have been identified using MALDI-MS and MS-MS. The finding that the expression level of differentially expressed proteins is preponderantly lower in the alcoholic brain is supported by recent results from parallel studies using microarray mRNA transcript.

Aged↗