Haptoglobin-α1, -α2, vitamin D-binding protein and apolipoprotein C-III as predictors of etanercept drug response in rheumatoid arthritis.

Introduction: The introduction of tumor necrosis factor-alpha (TNF-α) antagonists has substantially improved patient's clinical outcome in rheumatoid arthritis (RA). However, nearly 20% to 40% of RA patients do not respond to anti-TNF-α treatment strategies. To identify valid predictors of TNF-α antagonist response in RA, serum proteome profiles from responders (R) and non-responders (NR) to etanercept, a soluble recombinant TNF-α receptor/IgG Fc fusion protein receptor, were compared in a prospective cohort study.

NCAM and FGFR1 coexpression and colocalization in renal tumors.

Neural cell adhesion molecule (NCAM) and fibroblast growth factor receptor (FGFR) have a role in epithelial-mesenchymal transformation during tumor genesis. Interplay between both molecules activates FGFR signaling and it could be responsible for tumor development. Renal epithelial tumors were analyzed for FGFR1 and NCAM coexpression by immunohistochemistry and for colocalization of these molecules on the particular tumor cells by triple immunofluorescence.

Impaired immune defense in hemodialysis patients: role of α-defensins?

The mechanisms underlying the impaired immune response in hemodialysis (HD) patients are not completely understood. The α-defensins human neutrophil peptides-1, 2, and 3 are low molecular weight peptides with antimicrobial activity and important effector molecules of innate immune responses. We now examined the expression of these peptides in HD patients.

Secretion of ERP57 is important for extracellular matrix accumulation and progression of renal fibrosis, and is an early sign of disease onset.

Renal fibrosis is characterized by excessive accumulation of extracellular matrix (ECM), which compromises organ function by replacing normal organ tissue. The molecular mechanisms leading to renal fibrosis are not fully understood. Here we demonstrated that TGFβ1, AGT or PDGF stimulation of renal cells resulted in endoplasmic reticulum (ER) stress followed by activation of the protective unfolded protein response pathway and a high secretory level of protein disulfide isomerase ERP57 (also known as PDIA3).

Cathepsin D is present in human eccrine sweat and involved in the postsecretory processing of the antimicrobial peptide DCD-1L.

The protein pattern of healthy human eccrine sweat was investigated and 10 major proteins were detected from which apolipoprotein D, lipophilin B, and cathepsin D (CatD) were identified for the first time in human eccrine sweat. We focused our studies on the function of the aspartate protease CatD in sweat. In vitro digestion experiments using a specific fluorescent CatD substrate showed that CatD is enzymatically active in human sweat.

Differential detection of S100A8 in transitional cell carcinoma of the bladder by pair wise tissue proteomic and immunohistochemical analysis.

The search for novel molecular markers of tumor invasion is vital if strategies are to become more effective in the diagnostic and prognostic management of transitional cell carcinoma of the bladder. Up to 50% of tumors detected at stage 1 (pT1) progress to a higher grade even after endoscopic surgical resection, and there are currently no protein markers of this aggressive, invasive phenotype. We have combined SELDI-TOF-MS, ClinProt magnetic bead enrichment, Nano-LC-ESI-ion trap tandem mass spectrometry and immunohistochemical analysis to the study of 12 invasive bladder cancer tissue biopsies paired with normal bladder tissue samples obtained from the same patients for the definition and identification of proteins up-regulated in the tumors.

T cell epitope definition by differential mass spectrometry: identification of a novel, immunogenic HLA-B8 ligand directly from renal cancer tissue.

In this study, we describe a differential mass spectrometric technique for the immuno-proteomic analysis of the major histocompatibility complex (MHC) peptides of a renal cell carcinoma (RCC) biopsy compared with the healthy kidney tissue of the same patient after nephrectomy. Using a stable isotope labeling approach, we could directly compare and relatively quantify 43 MHC-peptide pairs, most of which were present in similar proportions on both normal kidney and tumor. Significantly, two dominant peptides of monoisotopic masses ([M+H](+)) 973.

Quantitative determination of the calcium channel antagonists amlodipine, lercanidipine, nitrendipine, felodipine, and lacidipine in human plasma using liquid chromatography-tandem mass spectrometry.

A sensitive and specific liquid chromatography-tandem mass spectrometric method has been developed and validated for the quantification of the five 1,4-dihydropyridine calcium channel antagonists amlodipine, lercanidipine, nitrendipine, felodipine, and lacidipine in human plasma. Sample preparation involved solid-phase extraction on RP-C18 cartridges with good recovery for all the compounds. Sample analysis was performed on a Luna RP-C18 analytical column (15 mm x 2 mm ID, 3.

Screening for dihydropyridine calcium channel blockers in plasma by automated solid-phase extraction and liquid chromatography/tandem mass spectrometry.

A liquid chromatographic/tandem mass spectrometric (LC/MS/MS) screening method was developed for the screening of 11 calcium channel blockers of the 1,4-dihydropyridine type in plasma samples for forensic and clinical cases. Plasma samples were extracted by automated solid-phase extraction. Analysis was performed using a reversed-phase C(18) column, gradient elution and a triple-quadrupole mass spectrometer with TurboIonSpray source in positive mode and multiple reaction monitoring.

Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients.

The molecular analysis of serum is an important field for the definition of potential diagnostic markers or disease-related protein alterations. Novel proteomic technologies such as the mass spectrometric-based surface-enhanced laser desorption/ionization (SELDI) ProteinChip technique facilitate a rapid and reproducible analysis of such protein mixtures and affords the researcher a new dimension in the search for biomarkers of disease. Here, we have applied this technology to the study of a cohort of serum samples from well-characterized renal cell carcinoma patients for the identification of such proteins by comparison to healthy controls.

Development of an MHC-class I peptide selection assay combining nanoparticle technology and matrix-assisted laser desorption/ionisation mass spectrometry.

Human leukocyte antigen (HLA)-bound peptides are central for recognition of infected/transformed cells by T cells, and have formed the basis for many immunotherapy strategies. Epitopes from a given protein sequence (e.g.

Detection of dermcidin-derived peptides in sweat by ProteinChip technology.

Recently, a novel antimicrobial peptide DCD-1, derived from the Dermcidin (DCD) gene and secreted by sweat glands, has been described by Schittek et al. [Nat. Immunol.

Expression of cadherin-8 in renal cell carcinoma and fetal kidney.

Cadherins represent a family of calcium-dependent cell adhesion molecules with an important regulatory function for maintenance of tissue architecture. Alterations of cadherin expression have been demonstrated in the development and progression of different epithelial tumors. In renal cell carcinoma (RCC), the majority of tumors express N-cadherin and cadherin-6.