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Quantitative proteomic analysis of microdissected breast cancer tissues : comparison of label-free and SILAC-based quantification with shotgun, directed, and targeted MS approaches

Quantitative proteomics plays an important role in validation of breast-cancer-related biomarkers. In this study, we systematically compared the performance of label-free quantification (LFQ) and SILAC with shotgun and directed methods for quantifying breast-cancer-related markers in microdissected tissues. We show that LFQ leads to slightly higher coefficient of variation (CV) for protein quantif

Comparative proteome analysis revealing an 11-protein signature for aggressive triple-negative breast cancer

BACKGROUND: Clinical outcome of patients with triple-negative breast cancer (TNBC) is highly variable. This study aims to identify and validate a prognostic protein signature for TNBC patients to reduce unnecessary adjuvant systemic therapy.METHODS: Frozen primary tumors were collected from 126 lymph node-negative and adjuvant therapy-naive TNBC patients. These samples were used for global proteom

Ferritin heavy chain in triple negative breast cancer : a favorable prognostic marker that relates to a cluster of differentiation 8 positive (CD8+) effector T-cell response

Ferritin heavy chain (FTH1) is a 21-kDa subunit of the ferritin complex, known for its role in iron metabolism, and which has recently been identified as a favorable prognostic protein for triple negative breast cancer (TNBC) patients. Currently, it is not well understood how FTH1 contributes to an anti-tumor response. Here, we explored whether expression and cellular compartmentalization of FTH1

5G : A tutorial overview of standards, trials, challenges, deployment, and practice

There is considerable pressure to define the key requirements of 5G, develop 5G standards, and perform technology trials as quickly as possible. Normally, these activities are best done in series but there is a desire to complete these tasks in parallel so that commercial deployments of 5G can begin by 2020. 5G will not be an incremental improvement over its predecessors; it aims to be a revolutio

Identification of high transverse momentum top quarks in pp collisions at √s= 8 TeV with the ATLAS detector

This paper presents studies of the performance of several jet-substructure techniques, which are used to identify hadronically decaying top quarks with high transverse momentum contained in large-radius jets. The efficiency of identifying top quarks is measured using a sample of top-quark pairs and the rate of wrongly identifying jets from other quarks or gluons as top quarks is measured using mul

Global proteomic characterization of microdissected estrogen receptor positive breast tumors

We here describe two proteomic datasets deposited in ProteomeXchange via PRIDE partner repository [1] with dataset identifiers PXD000484 (defined as "training") and PXD000485 (defined as "test") that have been used for the development of a tamoxifen outcome predictive signature [2]. Both datasets comprised 56 fresh frozen estrogen receptor (ER) positive primary breast tumor specimens derived from

4-protein signature predicting tamoxifen treatment outcome in recurrent breast cancer

Estrogen receptor (ER) positive tumors represent the majority of breast malignancies, and are effectively treated with hormonal therapies, such as tamoxifen. However, in the recurrent disease resistance to tamoxifen therapy is common and a major cause of death. In recent years, in-depth proteome analyses have enabled identification of clinically useful biomarkers, particularly, when heterogeneity

Annexin-A1 and caldesmon are associated with resistance to tamoxifen in estrogen receptor positive recurrent breast cancer

Tamoxifen therapy resistance constitutes a major cause of death in patients with recurrent estrogen receptor (ER) positive breast cancer. Through high resolution mass spectrometry (MS), we previously generated a 4-protein predictive signature for tamoxifen therapy outcome in recurrent breast cancer. ANXA1 and CALD1, which were not included in the classifier, were however the most differentially ex

Targeted MS Assay Predicting Tamoxifen Resistance in Estrogen-Receptor-Positive Breast Cancer Tissues and Sera

We recently reported on the development of a 4-protein-based classifier (PDCD4, CGN, G3BP2, and OCIAD1) capable of predicting outcome to tamoxifen treatment in recurrent, estrogen-receptor-positive breast cancer based on high-resolution MS data. A precise and high-throughput assay to measure these proteins in a multiplexed, targeted fashion would be favorable to measure large numbers of patient sa

The advantage of laser-capture microdissection over whole tissue analysis in proteomic profiling studies

Laser-capture microdissection (LCM) offers a reliable cell population enrichment tool and has been successfully coupled to MS analysis. Despite this, most proteomic studies employ whole tissue lysate (WTL) analysis in the discovery of disease biomarkers and in profiling analyses. Furthermore, the influence of tissue heterogeneity in WTL analysis, nor its impact in biomarker discovery studies have

Endocrine therapy resistance in estrogen receptor (ER)-positive breast cancer

Estrogen receptor (ER)-positive breast cancer represents the majority (∼70%) of all breast malignancies. In this subgroup of breast cancers, endocrine therapies are effective both in the adjuvant and recurrent settings, although resistance remains a major issue. Several high-throughput approaches have been used to elucidate mechanisms of resistance and to derive potential predictive markers or alt

Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients

We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin

Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer

In a previous study, we detected a significant association between phosphoserine aminotransferase 1 (PSAT1) hyper-methylation and mRNA levels to outcome to tamoxifen treatment in recurrent disease. We here aimed to study the association of PSAT1 protein levels to outcome upon tamoxifen treatment and to obtain more insight in its role in tamoxifen resistance. A cohort of ER positive, hormonal thera

Collective Action on Forest Governance: An Institutional Analysis of the Cambodian Community Forest System

Decentralisation in Cambodia has long been propagated as a means to enhance local engagement with governance structures. But in the forestry sector, even limited devolution of powers often constrains local user groups with excessive bureaucratic burdens. In addition, entrenched political economy interests tend to inhibit effective governance. To investigate the apparent institutional malaise that

Vertical Extension of Buildings

Many policy targets have been developed with the aim of reaching a more sustainable development; more specifically, thestudied policies target energy use and urban growth. For example, by 2050 the aim is that the European Union will havereduced its greenhouse emissions by 90%. Examples of policy targets regarding urban growth can be found in many ofthe larger cities, as they have developed plans fMany policy targets have been developed with the aim of reaching a more sustainable development; more specifically, thestudied policies target energy use and urban growth. For example, by 2050 the aim is that the European Union will havereduced its greenhouse emissions by 90%. Examples of policy targets regarding urban growth can be found in many ofthe larger cities, as they have developed plans f

Managers’ attitudes to their older employees - a cross-sectional study

BACKGROUND: Societal interest in enabling older workers to prolong their working life has increased in recent years due to demographic change. Managers have a key role in extending working life among employees, because they control the organisation, work environment and potential measures enabling older workers to extend their working life. OBJECTIVE: To examine managers' attitudes to their older

Time for Caring? Elderly care employees’ occupational activities in the cross draft between their work priorities, “must-do’s” and meaningfulness.

An increasing number of older people in the population will bring new challenges for the society and care coordination. One of the most important questions in care coordination is the employees’ work performance. The overall aim of this study was to examine care employees’ experience of factors that rule how they allocate their time and tasks in the care work. The study was qualitative and consist