Efficacy of Cetuximab in the Treatment of Ménétrier’s Disease

Fiske, William H.; Tanksley, Jarred; Nam, Ki Taek; Goldenring, James R.; Slebos, Robbert J.C.; Liebler, Daniel C.; Abtahi, Amir M.; Fleur, Bonnie La; Ayers, Gregory D.; Lind, Christopher R. P.; Washington, Mary Kay; Coffey, Robert J.

doi:10.1126/scitranslmed.3000320

Cited by 60 publications

(70 citation statements)

References 47 publications

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“…This approach has been successfully used for proteomic analysis not only of tissues (11)(12)(13)(14), but also of pleural fluid and plasma from lung cancer patients (15,16). The major advantage of this technique is sensitivity, with thousands of proteins directly identified in typical analyses (13).…”

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confidence: 99%

In-depth Proteomic Analysis of Nonsmall Cell Lung Cancer to Discover Molecular Targets and Candidate Biomarkers

Kikuchi

Hassanein

Amann

et al. 2012

Molecular & Cellular Proteomics

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Advances in proteomic analysis of human samples are driving critical aspects of biomarker discovery and the identification of molecular pathways involved in disease etiology. Toward that end, in this report we are the first to use a standardized shotgun proteomic analysis method for in-depth tissue protein profiling of the two major subtypes of nonsmall cell lung cancer and normal lung tissues. We identified 3621 proteins from the analysis of pooled human samples of squamous cell carcinoma, adenocarcinoma, and control specimens. In addition to proteins previously shown to be implicated in lung cancer, we have identified new pathways and multiple new differentially expressed proteins of potential interest as therapeutic targets or diagnostic biomarkers, including some that were not identified by transcriptome profiling. Up-regulation of these proteins was confirmed by multiple reaction monitoring mass spectrometry. A subset of these proteins was found to be detectable and differentially present in the peripheral blood of cases and matched controls. Label-free shotgun proteomic analysis allows definition of lung tumor proteomes, identification of biomarker candidates, and potential targets for therapy. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.015370, 916 -932, 2012.Lung cancer is one of the deadliest cancers, with ϳ200,000 newly diagnosed individuals and 160,000 deaths every year in the United States (1). Despite the most advanced treatments that modern medicine has to offer, the five-year survival rate remains less than 15%. Although a small subset of tumors have been found to be driven by single mutated oncogenes for which active, but still noncurative, therapies are available, the vast majority of patients have complex multifactorial disease with few effective therapeutic options. New early detection strategies and molecular therapeutic targets are urgently needed to improve patient survival.Genomic analysis has enabled us to measure the sequence, copy number, and expression changes of thousands of genes simultaneously, which can be used to discover transcripts specifically altered or expressed in tumor tissues (2-4). Although genomic studies have given important new insights into the mechanisms of carcinogenesis, therapeutic targets, and most practical biomarkers are their protein products, and the correlation between transcript sequence or level and protein function remains complex and poorly understood. Protein expression, in part, depends on transcript levels, but it is clear that significant translational and post-translational regulation of protein levels and function occurs, adding another level of complexity in the regulation of activity, especially in tumor cells (5, 6). It would be ideal to have a comprehensive understanding of the novel changes in protein expression levels and the modifications of proteins in cancer cells, but the technology to directly study proteomes has lagged behind that to assess genomes and transcriptomes. We and others have used matrix-assisted laser desorption and...

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confidence: 99%

In-depth Proteomic Analysis of Nonsmall Cell Lung Cancer to Discover Molecular Targets and Candidate Biomarkers

Kikuchi

Hassanein

Amann

et al. 2012

Molecular & Cellular Proteomics

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“…Se han utilizado tratamientos empí-ricos con antiácidos, anticolinérgicos, octreótido y prednisona, sin embargo, no existen evidencias sólidas de beneficios asociados a estas terapias 1,3,11 . La demostración del trastorno de señalización asociado a EGFR en la enfermedad de Ménétrier ha permitido el tratamiento con cetuximab, anticuerpo monoclonal que bloquea el sitio de unión de EGFR, con 7 casos comunicados en la literatura con respuesta favorable 11,12,18 . Sin embargo, el uso de cetuximab aún es considerado como tratamiento "compasivo" por parte de la FDA, por lo que el tratamiento de elección para la enfermedad de Ménétrier continúa siendo la gastrectomía total o parcial según el compromiso gástrico presente y las características clínicas.…”

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Enfermedad de Ménétrier con compromiso gástrico difuso y duodenal: Caso clínico

et al. 2012

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“…Therefore, patients with Ménétrier disease are treated with Cetuximab, a monoclonal antibody blocking EGFR signaling 9 . Nevertheless, the underlying molecular defect(s) that results in upregulation of TGF-α in Ménétrier disease is still unknown and TGF-α is not overexpressed elsewhere in the body of individuals with Ménétrier disease 3 .…”

Section: Textmentioning

confidence: 99%

“…4B). To determine whether MIB2 mutants affect cardiomyocyte proliferation, incorporation of thymidine analogue 5-ethynyl-2'-deoxyuridine (EdU) was evaluated 9 in cardiomyocytes transduced with AAV6 encoding wild-type or MIB2 variants. MIB2 WT increased the number EdU-positive and α-actinin-positive cells whereas MIB2 V742G variant decreased the number of proliferating rat cardiomyocytes ( Fig.…”

Section: Textmentioning

confidence: 99%