Abstract:
:This nonrandomized phase I/II trial assessed the efficacy/tolerability of imatinib plus panitumumab in patients affected by metastatic colorectal cancer (mCRC) after stratification to treatment by selection of activated imatinib drug targets using reverse-phase protein array (RPPA). mCRC patients presenting with a biopsiable liver metastasis were enrolled. Allocation to the experimental and control arms was established using functional pathway activation mapping of c-Kit, PDGFR, and c-Abl phosphorylation by RPPA. The experimental arm received run-in escalation therapy with imatinib followed by panitumumab. The control arm received panitumumab alone. Seven patients were enrolled in the study. For three of the seven patients, sequential pre- and post-treatment biopsies were used to evaluate the effect of the therapeutic compounds on the drug targets and substrates. A decrease in the activation level of the drug targets and downstream substrates was observed in two of three patients. Combination therapy increased the activation of the AKT-mTOR pathway and several receptor tyrosine kinases. This study proposes a novel methodology for stratifying patients to personalized treatment based on the activation level of the drug targets. This workflow provides the ability to monitor changes in the signaling pathways after the administration of targeted therapies and to identify compensatory mechanisms.
journal_name
J Proteome Resjournal_title
Journal of proteome researchauthors
Pierobon M,Silvestri A,Spira A,Reeder A,Pin E,Banks S,Parasido E,Edmiston K,Liotta L,Petricoin Edoi
10.1021/pr401267msubject
Has Abstractpub_date
2014-06-06 00:00:00pages
2846-55issue
6eissn
1535-3893issn
1535-3907journal_volume
13pub_type
杂志文章abstract::The Chromosome-Centric Human Proteome Project (C-HPP) aims to identify "missing" proteins in the neXtProt knowledgebase. We present an in-depth proteomics analysis of the human sperm proteome to identify testis-enriched missing proteins. Using protein extraction procedures and LC-MS/MS analysis, we detected 235 protei...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.6b00400
更新日期:2016-11-04 00:00:00
abstract::N-glycosylation of proteins is well known to occur at asparagine residues that fall within the canonical consensus sequence N-X-S/T but has also been identified at a small number of asparagine residues within N-X-C motifs, including the N491 residue of human serotransferrin. Here we report novel glycosylation sites wi...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.5b00733
更新日期:2016-07-01 00:00:00
abstract::Metabolic profiling technology, a massive information provider, has promoted the understanding of the metabolism of multicomponent medicines and its interactions with endogenous metabolites, which was previously a challenge in clarification. In this study, an untargeted GC/MS-based approach was employed to investigate...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.6b00015
更新日期:2016-06-03 00:00:00
abstract::While numerous strategies exist for biomarker discovery, the bottleneck to product development and routine use at the clinic is in the verification phase of candidate biomarkers. The aim of this study was to establish a robust and high-throughput product ion monitoring (PIM) assay that is potentially capable of rapidl...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr7005999
更新日期:2008-02-01 00:00:00
abstract::Reliable statistical validation of peptide and protein identifications is a top priority in large-scale mass spectrometry based proteomics. PeptideProphet is one of the computational tools commonly used for assessing the statistical confidence in peptide assignments to tandem mass spectra obtained using database searc...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr7006818
更新日期:2008-01-01 00:00:00
abstract::New mass-tagging reagents for quantitative proteomics measurements have been designed using solid phase peptide synthesis technology. The solid phase mass tags have been used to accurately measure the relative amounts of cysteine-containing peptides in model peptide mixtures as well as in mixtures of tryptic digests i...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr034081k
更新日期:2004-01-01 00:00:00
abstract::Novel biomarker verification assays are urgently required to improve the efficiency of biomarker development. Benefitting from lower development costs, multiple reaction monitoring (MRM) has been used for biomarker verification as an alternative to immunoassay. However, in general MRM analysis, only one sample can be ...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr4005025
更新日期:2013-09-06 00:00:00
abstract::We have obtained the first direct electrochemistry of full-length inducible nitric oxide synthase (iNOS) by entrapping the enzyme in polyethylenimine (PEI) film. The interaction between iNOS and calmodulin (CaM) was then studied, which revealed an enhanced electron-transfer reactivity of the enzyme facilitated by CaM....
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr060544l
更新日期:2007-04-01 00:00:00
abstract::Glycosylation is an abundant and important protein modification with large influence on the properties and interactions of glycoconjugates. Human plasma N-glycosylation has been the subject of frequent investigation, revealing strong associations with physiological and pathological conditions. Less well-characterized ...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.6b00071
更新日期:2016-10-07 00:00:00
abstract::The identification and the present wide acceptance of cardiovascular risk factors such as age, sex, hypertension, hyperlipidemia, smoking, obesity, diabetes, and physical inactivity have led to dramatic reductions in cardiovascular morbidity and mortality. However, novel risk predictors present opportunities to identi...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr200452j
更新日期:2011-11-04 00:00:00
abstract::Microorganisms release effector molecules that modulate the host machinery enabling survival, replication, and dissemination of a pathogen. Here we characterized the extracellular proteome of Paracoccidioides brasiliensis at its pathogenic yeast phase. Cell-free culture supernatants from the Pb18 isolate, cultivated i...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr200872s
更新日期:2012-03-02 00:00:00
abstract::Campylobacter jejuni, an important foodborne microorganism, poses severe and emergent threats to human health as antibiotic resistance becomes increasingly prevalent. The mechanisms of drug resistance are hard to decipher, and little is known at the metabolic level. Here we apply metabolomic profiling to discover meta...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr501061d
更新日期:2015-02-06 00:00:00
abstract::Autosomal dominant polycystic liver disease (PCLD) is characterized by multiple liver cysts and is caused by mutations in PRKCSH (hepatocystin). Mechanisms of cystogenesis are unknown, but previous studies have shown that hepatocystin is secreted in vitro. The goal of this study was to determine the fate of hepatocyst...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr8000282
更新日期:2008-06-01 00:00:00
abstract::The chromatophore membrane of the photosynthetic diazotroph Rhodospirillum rubrum is of vital importance for a number of central processes, including nitrogen fixation. Using a novel amphiphile, we have identified protein complexes present under different nitrogen availability conditions by the use of two-dimensional ...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr100838x
更新日期:2011-06-03 00:00:00
abstract::As a potential tool for proteomics and protein characterization, in-gel cysteine- and arginine-specific cleavage is demonstrated by means of trypsin or endoproteinase Lys-C for six model proteins (lysozyme, alpha-lactalbumin, beta-lactoglobulin, ribonuclease A, albumin, and transferrin), ranging in size from 14 kDa to...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr025568g
更新日期:2003-03-01 00:00:00
abstract::We present a novel straightforward method for enrichment of N-terminal peptides, utilizing charge-based fractional diagonal chromatography (ChaFRADIC). Our method is robust, easy to operate, fast, specific, and more sensitive than existing methods, enabling the differential quantitation of 1459 nonredundant N-terminal...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr400435d
更新日期:2013-09-06 00:00:00
abstract::Plasma biomarkers of exposure to environmental contaminants play an important role in early detection of disease. The emerging field of proteomics presents an attractive opportunity for candidate biomarker discovery, as it simultaneously measures and analyzes a large number of proteins. This article presents a case st...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr070491n
更新日期:2008-01-01 00:00:00
abstract::Sterols are membrane-bound isoprenoid lipids that are required for cell viability and growth. In plants, it is generally assumed that 3-hydroxy-3-methylglutaryl-CoA-reductase (HMGR) is a key element of their biosynthesis, but the molecular regulation of that pathway is largely unknown. In an attempt to identify regula...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr201127u
更新日期:2012-02-03 00:00:00
abstract::Cripto is one of the key regulators of embryonic stem cells (ESCs) differentiation into cardiomyocites vs neuronal fate. Cripto(-/-) murine ESCs have been utilized to investigate the molecular mechanisms underlying early events of mammalian lineage differentiation. 2D/LC-MS/MS and a label-free LC-MS approaches were us...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr800485c
更新日期:2009-02-01 00:00:00
abstract::To assess the global effect of preterm birth on fetal metabolism and maternal-fetal nutrient transfer, we used a mass spectrometric-based chemical phenotyping approach on cord blood obtained at the time of birth. We sampled umbilical venous, umbilical arterial, and maternal blood from mothers delivering very-low birth...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr400122v
更新日期:2013-06-07 00:00:00
abstract::The purpose of this study was to determine the system-wide consequences of deficiencies in two essential micronutrients, vitamins E and C, on the proteome using zebrafish (Danio rerio) as one of the few vertebrate models that similar to humans cannot synthesize vitamin C. We describe a label-free proteomics workflow t...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr401108d
更新日期:2014-03-07 00:00:00
abstract::Gas chromatography-mass spectrometry (GC-MS) platforms are typically run in electron ionization (EI) mode for mass spectral matching and metabolite annotation. With the advent of high resolution mass spectrometry (HRMS), soft ionization techniques such as chemical ionization (CI) may provide additional coverage for co...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.9b00774
更新日期:2020-07-02 00:00:00
abstract::We undertook an unbiased metabolite profiling of fibroblasts from schizophrenia patients and healthy controls to identify metabolites and pathways that are dysregulated in disease, seeking to gain new insights into the disease biology of schizophrenia and to discover potential disease-related biomarkers. We measured p...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.6b00628
更新日期:2017-02-03 00:00:00
abstract::Sardinian alcohol-preferring (sP) and Sardinian alcohol-non preferring (sNP) rats have been selectively bred for opposite alcohol preference and consumption. Aiming to verify possible differences at the proteomics level between sP and sNP rats, we investigated the salivary proteome by a a liquid chromatography-mass sp...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.7b00632
更新日期:2018-01-05 00:00:00
abstract::Deamidation of asparaginyl residues in proteins produces a mixture of asparaginyl, n-aspartyl, and isoaspartyl residues, which affects the proteins' structure, function, and stability. Thus, it is important to identify and quantify the products to evaluate the effects in biological systems. It is still a challenging t...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr201048c
更新日期:2012-03-02 00:00:00
abstract::Plastids are essential organelles because they contribute to primary and secondary metabolism and plant signaling networks. A high-quality inventory of the plastid proteome is therefore a critical tool in plant research. We present reference plastid proteomes for maize (Zea mays) and Arabidopsis (Arabidopsis thaliana)...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr300952g
更新日期:2013-01-04 00:00:00
abstract::We demonstrate an approach for global quantitative analysis of protein mixtures using differential stable isotopic labeling of the enzyme-digested peptides combined with microbore liquid chromatography (LC) matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS). Microbore LC provides higher sample ...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr049784w
更新日期:2005-05-01 00:00:00
abstract::Coronary artery disease is one of the most frequent causes of morbidity and mortality worldwide. It is even more prevalent in patients with type 2 diabetes mellitus who suffer from obesity and increased accumulation of epicardial fat with a possible contributing role in the development of coronary artery disease. We p...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.0c00269
更新日期:2020-10-02 00:00:00
abstract::Hepatocellular carcinoma (HCC) remains as the fifth most common cancer in the world and accounts for more than 700,000 deaths annually. Changes in serum glycosylation have long been associated with this cancer but the source of that material is unknown and direct glycan analysis of HCC tissues has been limited. Our la...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/acs.jproteome.8b00323
更新日期:2018-10-05 00:00:00
abstract::This study presents a comparative proteomic analysis of the membrane subproteome of whole Arabidopsis seedlings using 2% Brij-58 or 60% methanol to enrich and solubilize membrane proteins for strong cation exchange fractionation and reversed-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 4...
journal_title:Journal of proteome research
pub_type: 杂志文章
doi:10.1021/pr060525b
更新日期:2007-05-01 00:00:00