Current methods of protein detection are insensitive to detecting subtle changes in oncoprotein activation that underlie key cancer signaling processes. The requirement for large numbers of cells precludes serial tumor sampling for assessing a response to therapeutics. Therefore, we have developed a nanofluidic proteomic immunoassay (NIA) to quantify total and low-abundance protein isoforms in nanoliter volumes. Our method can quantify amounts of MYC oncoprotein and B cell lymphoma protein-2 (BCL2) in Burkitt's and follicular lymphoma; identify changes in activation of extracellular signal-related kinases-1 (ERK1) and ERK2, mitogen-activated kinase-1 (MEK), signal transducer and activator of transcription protein-3 (STAT3) and STAT5, c-Jun N-terminal kinase (JNK) and caspase-3 in imatinib-treated chronic myelogeneous leukemia (CML) cells; measure an unanticipated change in the phosphorylation of an ERK2 isomer in individuals with CML who responded to imatinib; and detect a decrease in STAT3 and STAT5 phosphorylation in individuals with lymphoma who were treated with atorvastatin. Therefore, we have described a new and highly sensitive method for determining oncoprotein expression and phosphorylation in clinical specimens for the development of new therapeutics for cancer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006986 | PMC |
| http://dx.doi.org/10.1038/nm.1903 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cellulose Nanocrystal Composite Membrane Enhanced with In Situ Grown Metal-Organic Frameworks for Osmotic Energy Conversion.
Small
November 2024
State Key Laboratory of Medical Proteomics, National Chromatographic R. & A. Center, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, P. R. China.
Access to clean and renewable energy, osmotic energy from salinity gradient difference, for example, is central to the sustainability of human civilization. Despite numerous examples of nanofluidic membranes for osmotic energy conversion, one produced from abundant and renewable biomass resources remains largely unexplored. In this work, cotton-derived cellulose nanocrystals (CNCs) are employed to fabricate a membrane by self-assembly with polyvinyl alcohol (PVA) and subsequent in situ growth of metal-organic framework (MOF), UiO-66-(COOH), to provide an example.
View Article and Find Full Text PDFDesign Principles of DNA-Barcodes for Nanopore-FET Readout, Based on Molecular Dynamics and TCAD Simulations.
J Phys Chem A
May 2024
Imec, Kapeldreef 75, B-3001 Leuven, Belgium.
Nanopore field-effect transistor (NP-FET) devices hold great promise as sensitive single-molecule sensors, which provide CMOS-based on-chip readout and are also highly amenable to parallelization. A plethora of applications will therefore benefit from NP-FET technology, such as large-scale molecular analysis (e.g.
View Article and Find Full Text PDFNanofluidic Device for Detection of Lysine Methylpeptides and Sensing of Lysine Methylation.
Anal Chem
May 2023
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, P. R. China.
Article Synopsis
- Protein methylation is a crucial but challenging post-translational modification that requires effective detection tools.
- A new nanofluidic electric sensing device uses a specialized nanochannel with a functionalized molecule to selectively identify lysine methylpeptides at very low concentrations and differentiate between their methylation states.
- This innovative device can monitor lysine methylation processes in real time and may lead to advancements in assays for studying protein modifications.
Single-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore.
Nat Commun
April 2023
Disease Target Structure Research Center, Division of Biomedical Research, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
In drug discovery, efficient screening of protein-drug interactions (PDIs) is hampered by the limitations of current biophysical approaches. Here, we develop a biological nanopore sensor for single-molecule detection of proteins and PDIs using the pore-forming toxin YaxAB. Using this YaxAB nanopore, we demonstrate label-free, single-molecule detection of interactions between the anticancer Bcl-xL protein and small-molecule drugs as well as the Bak-BH3 peptide.
View Article and Find Full Text PDFStability of enzyme immobilized on the nanofluidic channel surface.
Anal Sci
March 2023
Institute of Nanoengineering and Microsystems, Department of Power Mechanical Engineering, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, 300044, Taiwan, Republic of China.
The lifetime of an enzyme is critical to prevent system failure and optimize maintenance schedules in biological and analytical chemistry. The lifetime metrics of an enzyme can be evaluated from enzyme activity in terms of catalytic cycles per enzyme at various storage times. Trypsin, which is a gold-standard enzyme in proteomics, has been known to decrease activity due to self-digestion.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!