Risk assessment of disease recurrence in early breast cancer: A serum metabolomic study focused on elderly patients.

Background: We previously showed that metabolomics predicts relapse in early breast cancer (eBC) patients, unselected by age. This study aims to identify a "metabolic signature" that differentiates eBC from advanced breast cancer (aBC) patients, and to investigate its potential prognostic role in an elderly population.

Methods: Serum samples from elderly breast cancer (BC) patients enrolled in 3 onco-geriatric trials, were retrospectively analyzed via proton nuclear magnetic resonance (1H NMR) spectroscopy.

Circulating tumor cells and palbociclib treatment in patients with ER-positive, HER2-negative advanced breast cancer: results from a translational sub-study of the TREnd trial.

Background: Circulating tumor cells (CTCs) are prognostic in patients with advanced breast cancer (ABC). However, no data exist about their use in patients treated with palbociclib. We analyzed the prognostic role of CTC counts in patients enrolled in the cTREnd study, a pre-planned translational sub-study of TREnd (NCT02549430), that randomized patients with ABC to palbociclib alone or palbociclib plus the endocrine therapy received in the prior line of treatment.

The Effect of Casein Protein Prior to Sleep on Fat Metabolism in Obese Men.

We have previously shown that ingesting protein at night before sleep is either beneficial or non-detrimental to metabolism, health, and body composition in obese women. However, the overnight protein-induced lipolytic actions and mechanism for improved metabolism and body composition have not been fully established. Therefore, in a crossover design, twelve obese men (age, 27.

ROCK1 is a potential combinatorial drug target for BRAF mutant melanoma.

Treatment of BRAF mutant melanomas with specific BRAF inhibitors leads to tumor remission. However, most patients eventually relapse due to drug resistance. Therefore, we designed an integrated strategy using (phospho)proteomic and functional genomic platforms to identify drug targets whose inhibition sensitizes melanoma cells to BRAF inhibition.

Protein acetylation affects acetate metabolism, motility and acid stress response in Escherichia coli.

Although protein acetylation is widely observed, it has been associated with few specific regulatory functions making it poorly understood. To interrogate its functionality, we analyzed the acetylome in Escherichia coli knockout mutants of cobB, the only known sirtuin-like deacetylase, and patZ, the best-known protein acetyltransferase. For four growth conditions, more than 2,000 unique acetylated peptides, belonging to 809 proteins, were identified and differentially quantified.

Serum metabolomic profiles evaluated after surgery may identify patients with oestrogen receptor negative early breast cancer at increased risk of disease recurrence. Results from a retrospective study.

Purpose: Metabolomics is a global study of metabolites in biological samples. In this study we explored whether serum metabolomic spectra could distinguish between early and metastatic breast cancer patients and predict disease relapse.

Methods: Serum samples were analysed from women with metastatic (n = 95) and predominantly oestrogen receptor (ER) negative early stage (n = 80) breast cancer using high resolution nuclear magnetic resonance spectroscopy.

Evaluation of the cardiovascular health study (CHS) instrument and the Vulnerable Elders Survey-13 (VES-13) in elderly cancer patients. Are we still missing the right screening tool?

Background: A geriatric screening tool would be valuable to identify elderly cancer patients who might benefit from a comprehensive geriatric assessment (CGA). This study evaluated the accuracy of the cardiovascular health study (CHS) instrument in predicting abnormality in CGA. The vulnerable elders' survey-13 (VES-13) was also evaluated.

Deep proteome profiling of circulating granulocytes reveals bactericidal/permeability-increasing protein as a biomarker for severe atherosclerotic coronary stenosis.

Coronary atherosclerosis represents the major cause of death in Western societies. As atherosclerosis typically progresses over years without giving rise to clinical symptoms, biomarkers are urgently needed to identify patients at risk. Over the past decade, evidence has accumulated suggesting cross-talk between the diseased vasculature and cells of the innate immune system.

Current challenges in software solutions for mass spectrometry-based quantitative proteomics.

Mass spectrometry-based proteomics has evolved as a high-throughput research field over the past decade. Significant advances in instrumentation, and the ability to produce huge volumes of data, have emphasized the need for adequate data analysis tools, which are nowadays often considered the main bottleneck for proteomics development. This review highlights important issues that directly impact the effectiveness of proteomic quantitation and educates software developers and end-users on available computational solutions to correct for the occurrence of these factors.

Exploration of serum metabolomic profiles and outcomes in women with metastatic breast cancer: a pilot study.

Background: Metabolomics, a global study of metabolites and small molecules, is a novel expanding field. In this pilot study, metabolomics has been applied to serum samples from women with metastatic breast cancer to explore outcomes and response to treatment.

Patients And Methods: Pre-treatment and serial on-treatment serum samples were available from an international clinical trial in which 579 women with metastatic breast cancer were randomized to paclitaxel plus either a targeted anti-HER2 treatment (lapatinib) or placebo.

Applications of stable isotope dimethyl labeling in quantitative proteomics.

Mass spectrometry has proven to be an indispensable tool for protein identification, characterization, and quantification. Among the possible methods in quantitative proteomics, stable isotope labeling by using reductive dimethylation has emerged as a cost-effective, simple, but powerful method able to compete at any level with the present alternatives. In this review, we briefly introduce experimental and software methods for proteome analysis using dimethyl labeling and provide a comprehensive overview of reported applications in the analysis of (1) differential protein expression, (2) posttranslational modifications, and (3) protein interactions.

Inter- and intra-tumoral heterogeneity in DNA damage evaluated by comet assay in early breast cancer patients.

There are no clinical tools to functionally assess degree of DNA damage in breast cancer. The comet assay is an accepted research tool for assessing DNA damage, however, most cancer studies have assessed lymphocytes as surrogate cells. The aim of this pilot study was to use the comet assay in early breast cancer directly in tumor tissue to compare DNA damage between and within traditionally defined subgroups, and to explore intra-tumoral heterogeneity.

Reorganized PKA-AKAP associations in the failing human heart.

Here we reveal that the characterization of large-scale re-arrangements of signaling scaffolds induced by heart failure can serve as a novel concept to identify more specific therapeutic targets. In the mammalian heart, the cAMP pathway, with the cAMP-dependent protein kinase (PKA) in a central role, acts directly downstream of adrenergic receptors to mediate cardiac contractility and rhythm. Heart failure, characterized by severe alterations in adrenergic stimulation is, amongst other interventions, often treated with β-blockers.

Deconvolution of overlapping isotopic clusters improves quantification of stable isotope-labeled peptides.

High-resolution mass spectrometry and the use of stable isotopes have greatly improved our ability to quantify proteomes. Typically, the relative abundance of peptides is estimated by identifying the isotopic clusters and by comparing the peak intensities of peptide pairs. However, when the mass shift between the labeled peptides is small, there can be the possibility for overlap of the isotopic clusters which will hamper quantification accuracy with a typical upwards bias for the heavier peptide.

Identification of a serum-detectable metabolomic fingerprint potentially correlated with the presence of micrometastatic disease in early breast cancer patients at varying risks of disease relapse by traditional prognostic methods.

Background: Prognostic tools in early breast cancer are inadequate. The evolving field of metabolomics may allow more accurate identification of patients with residual micrometastases.

Patients And Methods: Forty-four early breast cancer patients with pre- and postoperative serum samples had metabolomic assessment by nuclear magnetic resonance.

Uncovering the metabolomic fingerprint of breast cancer.

Metabolomics, the study of metabolites and small intermediate molecules, may play a key role in further elucidation of breast cancer. This dynamic, simultaneous assessment of thousands of metabolites allows identification of the presence, concentration and fluxes of specific metabolites, and recognition of the critical metabolic pathways recruited in carcinogenesis. Studies of tumour cell and tissue allow focused analysis on the tumour, whilst studies of biofluids have the appeal of concurrent assessment of tumour and host.

Improved label-free LC-MS analysis by wavelet-based noise rejection.

Label-free LC-MS analysis allows determining the differential expression level of proteins in multiple samples, without the use of stable isotopes. This technique is based on the direct comparison of multiple runs, obtained by continuous detection in MS mode. Only differentially expressed peptides are selected for further fragmentation, thus avoiding the bias toward abundant peptides typical of data-dependent tandem MS.

Quantification of membrane proteins using nonspecific protease digestions.

We present a mass spectrometry-based method for the identification and quantification of membrane proteins using the low-specificity protease Proteinase K, at very high pH, to digest proteins isolated by a modified SDS-PAGE protocol. The resulting peptides are modified with a fragmentation-directing isotope labeled tag. We apply the method to quantify differences in membrane protein expression of Bacillus subtilis grown in the presence or absence of glucose.

Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients.

Biocharacterization of circulating tumor cells (CTCs) in the peripheral blood of advanced breast cancer (ABC) patients may represent a real-time tumor biopsy. We assessed HER2 status on CTCs from blood samples of ABC patients. CTCs were separated and stained using the CellSearch System((R)).

Wavelet-based method for noise characterization and rejection in high-performance liquid chromatography coupled to mass spectrometry.

We present a new method for rejecting noise from HPLC-MS data sets. The algorithm reveals peptides at low concentrations by minimizing both the chemical and the random noise. The goal is reached through a systematic approach to characterize and remove the background.

Replicating neuroblastoma cells in different cell cycle phases display different vulnerability to amyloid toxicity.

A key role of mitotic activation in neuronal cell death in early stages of Alzheimer's disease (AD) has been suggested. Apparently, terminally differentiated neurons are precluded from mitotic division, yet some phenotypic markers of cell cycling are present in AD-vulnerable brain areas. In this paper, we investigated whether dividing human neuroblastoma cells are preferentially vulnerable to amyloid aggregate toxicity in some specific cell cycle stage(s).