Pilot phase I/II personalized therapy trial for metastatic colorectal cancer: evaluating the feasibility of protein pathway activation mapping for stratifying patients to therapy with imatinib and panitumumab.

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 Res

authors

Pierobon M,Silvestri A,Spira A,Reeder A,Pin E,Banks S,Parasido E,Edmiston K,Liotta L,Petricoin E

doi

10.1021/pr401267m

subject

Has Abstract

pub_date

2014-06-06 00:00:00

pages

2846-55

issue

6

eissn

1535-3893

issn

1535-3907

journal_volume

13

pub_type

杂志文章
  • Looking for Missing Proteins in the Proteome of Human Spermatozoa: An Update.

    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

    authors: Vandenbrouck Y,Lane L,Carapito C,Duek P,Rondel K,Bruley C,Macron C,Gonzalez de Peredo A,Couté Y,Chaoui K,Com E,Gateau A,Hesse AM,Marcellin M,Méar L,Mouton-Barbosa E,Robin T,Burlet-Schiltz O,Cianferani S,Ferro M,Fr

    更新日期:2016-11-04 00:00:00

  • Identification of Novel N-Glycosylation Sites at Noncanonical Protein Consensus Motifs.

    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

    authors: Lowenthal MS,Davis KS,Formolo T,Kilpatrick LE,Phinney KW

    更新日期:2016-07-01 00:00:00

  • Metabonomics Approach to Assessing the Metabolism Variation and Endoexogenous Metabolic Interaction of Ginsenosides in Cold Stress Rats.

    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

    authors: Zhang Z,Wang X,Wang J,Jia Z,Liu Y,Xie X,Wang C,Jia W

    更新日期:2016-06-03 00:00:00

  • "Product ion monitoring" assay for prostate-specific antigen in serum using a linear ion-trap.

    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

    authors: Kulasingam V,Smith CR,Batruch I,Buckler A,Jeffery DA,Diamandis EP

    更新日期:2008-02-01 00:00:00

  • Statistical validation of peptide identifications in large-scale proteomics using the target-decoy database search strategy and flexible mixture modeling.

    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

    authors: Choi H,Ghosh D,Nesvizhskii AI

    更新日期:2008-01-01 00:00:00

  • A simple solid phase mass tagging approach for quantitative proteomics.

    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

    authors: Shi Y,Xiang R,Crawford JK,Colangelo CM,Horváth C,Wilkins JA

    更新日期:2004-01-01 00:00:00

  • Hyperplex-MRM: a hybrid multiple reaction monitoring method using mTRAQ/iTRAQ labeling for multiplex absolute quantification of human colorectal cancer biomarker.

    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

    authors: Yin HR,Zhang L,Xie LQ,Huang LY,Xu Y,Cai SJ,Yang PY,Lu HJ

    更新日期:2013-09-06 00:00:00

  • Interaction between inducible nitric oxide synthase and calmodulin in Ca2+-free and -bound forms.

    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

    authors: Xiao H,Zhou H,Chen G,Liu S,Li G

    更新日期:2007-04-01 00:00:00

  • Murine Plasma N-Glycosylation Traits Associated with Sex and Strain.

    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

    authors: Reiding KR,Hipgrave Ederveen AL,Rombouts Y,Wuhrer M

    更新日期:2016-10-07 00:00:00

  • The cardiovascular risk of healthy individuals studied by NMR metabonomics of plasma samples.

    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

    authors: Bernini P,Bertini I,Luchinat C,Tenori L,Tognaccini A

    更新日期:2011-11-04 00:00:00

  • Vesicle and vesicle-free extracellular proteome of Paracoccidioides brasiliensis: comparative analysis with other pathogenic fungi.

    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

    authors: Vallejo MC,Nakayasu ES,Matsuo AL,Sobreira TJ,Longo LV,Ganiko L,Almeida IC,Puccia R

    更新日期:2012-03-02 00:00:00

  • Untargeted metabolomic profiling of amphenicol-resistant Campylobacter jejuni by ultra-high-performance liquid chromatography-mass spectrometry.

    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

    authors: Li H,Xia X,Li X,Naren G,Fu Q,Wang Y,Wu C,Ding S,Zhang S,Jiang H,Li J,Shen J

    更新日期:2015-02-06 00:00:00

  • Hepatocystin is not secreted in cyst fluid of hepatocystin mutant polycystic liver patients.

    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

    authors: Waanders E,Lameris AL,Op den Camp HJ,Pluk W,Gloerich J,Strijk SP,Drenth JP

    更新日期:2008-06-01 00:00:00

  • Identification of chromatophore membrane protein complexes formed under different nitrogen availability conditions in Rhodospirillum rubrum.

    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

    authors: Selao TT,Branca R,Chae PS,Lehtiö J,Gellman SH,Rasmussen SG,Nordlund S,Norén A

    更新日期:2011-06-03 00:00:00

  • In-gel derivatization of proteins for cysteine-specific cleavages and their analysis by mass spectrometry.

    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

    authors: Thevis M,Ogorzalek Loo RR,Loo JA

    更新日期:2003-03-01 00:00:00

  • Novel highly sensitive, specific, and straightforward strategy for comprehensive N-terminal proteomics reveals unknown substrates of the mitochondrial peptidase Icp55.

    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

    authors: Venne AS,Vögtle FN,Meisinger C,Sickmann A,Zahedi RP

    更新日期:2013-09-06 00:00:00

  • Biomarker discovery for arsenic exposure using functional data. Analysis and feature learning of mass spectrometry proteomic data.

    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

    authors: Harezlak J,Wu MC,Wang M,Schwartzman A,Christiani DC,Lin X

    更新日期:2008-01-01 00:00:00

  • Phosphoproteome exploration reveals a reformatting of cellular processes in response to low sterol biosynthetic capacity in Arabidopsis.

    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

    authors: Heintz D,Gallien S,Compagnon V,Berna A,Suzuki M,Yoshida S,Muranaka T,Van Dorsselaer A,Schaeffer C,Bach TJ,Schaller H

    更新日期:2012-02-03 00:00:00

  • Qualitative and quantitative proteomic profiling of cripto(-/-) embryonic stem cells by means of accurate mass LC-MS analysis.

    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

    authors: Chambery A,Vissers JP,Langridge JI,Lonardo E,Minchiotti G,Ruvo M,Parente A

    更新日期:2009-02-01 00:00:00

  • Maternal and cord blood LC-HRMS metabolomics reveal alterations in energy and polyamine metabolism, and oxidative stress in very-low birth weight infants.

    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

    authors: Alexandre-Gouabau MC,Courant F,Moyon T,Küster A,Le Gall G,Tea I,Antignac JP,Darmaun D

    更新日期:2013-06-07 00:00:00

  • Proteome-driven elucidation of adaptive responses to combined vitamin E and C deficiency in zebrafish.

    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

    authors: Motorykin I,Traber MG,Tanguay RL,Maier CS

    更新日期:2014-03-07 00:00:00

  • High Resolution GC-Orbitrap-MS Metabolomics Using Both Electron Ionization and Chemical Ionization for Analysis of Human Plasma.

    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

    authors: Misra BB,Olivier M

    更新日期:2020-07-02 00:00:00

  • Unbiased Metabolite Profiling of Schizophrenia Fibroblasts under Stressful Perturbations Reveals Dysregulation of Plasmalogens and Phosphatidylcholines.

    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

    authors: Huang JH,Park H,Iaconelli J,Berkovitch SS,Watmuff B,McPhie D,Öngür D,Cohen BM,Clish CB,Karmacharya R

    更新日期:2017-02-03 00:00:00

  • Marked Differences in the Submandibular Salivary Proteome between Sardinian Alcohol-Preferring and Sardinian Alcohol-Non Preferring Rats Revealed by an Integrated Top-Down-Bottom-Up Proteomic Platform.

    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

    authors: Cabras T,D'Alessandro A,Serrao S,Isola R,Iavarone F,Vincenzoni F,Colombo G,Ekström J,Messana I,Castagnola M

    更新日期:2018-01-05 00:00:00

  • Enhanced separation and characterization of deamidated peptides with RP-ERLIC-based multidimensional chromatography coupled with tandem mass spectrometry.

    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

    authors: Hao P,Qian J,Dutta B,Cheow ES,Sim KH,Meng W,Adav SS,Alpert A,Sze SK

    更新日期:2012-03-02 00:00:00

  • Construction of plastid reference proteomes for maize and Arabidopsis and evaluation of their orthologous relationships; the concept of orthoproteomics.

    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

    authors: Huang M,Friso G,Nishimura K,Qu X,Olinares PD,Majeran W,Sun Q,van Wijk KJ

    更新日期:2013-01-04 00:00:00

  • Quantitative proteome analysis using differential stable isotopic labeling and microbore LC-MALDI MS and MS/MS.

    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

    authors: Ji C,Li L

    更新日期:2005-05-01 00:00:00

  • Lipid Profiling in Epicardial and Subcutaneous Adipose Tissue of Patients with Coronary Artery Disease.

    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

    authors: Tomášová P,Čermáková M,Pelantová H,Vecka M,Kratochvílová H,Lipš M,Lindner J,Ivák P,Netuka I,Šedivá B,Haluzík M,Kuzma M

    更新日期:2020-10-02 00:00:00

  • N-Linked Glycan Branching and Fucosylation Are Increased Directly in Hcc Tissue As Determined through in Situ Glycan Imaging.

    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

    authors: West CA,Wang M,Herrera H,Liang H,Black A,Angel PM,Drake RR,Mehta AS

    更新日期:2018-10-05 00:00:00

  • Membrane proteomic analysis of Arabidopsis thaliana using alternative solubilization techniques.

    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

    authors: Mitra SK,Gantt JA,Ruby JF,Clouse SD,Goshe MB

    更新日期:2007-05-01 00:00:00