Nanofluidic proteomic assay for serial analysis of oncoprotein activation in clinical specimens
Alice C. Fan,Debabrita Deb-Basu,Mathias W. Orban,Jason Gotlib,Yasodha Natkunam,Roger A. O'Neill,Rose Ann Padua,Liwen Xu,Daryl Taketa,Amy E. Shirer,Shelly Beer,Ada X Yee,David Voehringer,Dean W. Felsher +13 more
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TLDR
A nanofluidic proteomic immunoassay (NIA) to quantify total and low-abundance protein isoforms in nanoliter volumes for the development of new therapeutics for cancer.Abstract:
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.read more
Citations
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Journal ArticleDOI
Chronic myeloid leukemia: mechanisms of blastic transformation
TL;DR: The BCR-ABL1 oncoprotein transforms pluripotent HSCs and initiates chronic myeloid leukemia (CML), which has been subclassified as either accelerated phase or blastic phase disease.
Journal ArticleDOI
The epichaperome is an integrated chaperome network that facilitates tumour survival
Anna Rodina,Tai Wang,Pengrong Yan,Erica DaGama Gomes,Mark Dunphy,Nagavarakishore Pillarsetty,John Koren,John F. Gerecitano,Tony Taldone,Hongliang Zong,Eloisi Caldas-Lopes,Mary L. Alpaugh,Adriana D. Corben,Matthew Riolo,Brad Beattie,Christina Pressl,Radu I Peter,Chao Xu,Robert Trondl,Hardik J. Patel,Fumiko Shimizu,Alexander Bolaender,Chenghua Yang,Palak Panchal,Mohammad F. Farooq,Sarah Kishinevsky,Shanu Modi,Oscar Lin,Feixia Chu,Sujata Patil,Hediye Erdjument-Bromage,Pat Zanzonico,Clifford A. Hudis,Lorenz Studer,Gail J. Roboz,Ethel Cesarman,Leandro Cerchietti,Ross L. Levine,Ari Melnick,Steven M. Larson,Jason S. Lewis,Monica L. Guzman,Gabriela Chiosis,Gabriela Chiosis +43 more
TL;DR: It is found that under conditions of stress, such as malignant transformation fuelled by MYC, the chaperome becomes biochemically ‘rewired’ to form a network of stable, survival-facilitating, high-molecular-weight complexes.
Patent
Slip chip device and methods
Rustem F. Ismagilov,Wenbin Du,Liang Li,Feng Shen,Kevin P. Nichols,Delai Chen,Jason E. Kreutz +6 more
TL;DR: In this article, a first surface having a plurality of first areas and a second surface having plurality of second areas is described, where the first surface and the second surface are opposed to one another and can move relative to each other.
Journal ArticleDOI
Microfluidic Western blotting
Alex J. Hughes,Amy E. Herr +1 more
TL;DR: The μWestern blot establishes a foundation for rapid, targeted proteomics by merging exceptional specificity with the throughput advantages of multiplexing, as is relevant to a broad range of biological inquiry.
Journal ArticleDOI
Circulating Lamin B1 (LMNB1) biomarker detects early stages of liver cancer in patients.
TL;DR: Li et al. as discussed by the authors employed a proteomic expression profiling approach to identify biomarkers for early stages of hepatocellular carcinoma (HCC) and subsequently assessed the clinical feasibility of a novel marker in plasma.
References
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Journal ArticleDOI
Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia
Brian J. Druker,Moshe Talpaz,Debra Resta,Bin Peng,Elisabeth Buchdunger,John Ford,Nicholas B. Lydon,Hagop M. Kantarjian,Renaud Capdeville,Sayuri Ohno-Jones,Charles L. Sawyers +10 more
TL;DR: STI571 is well tolerated and has significant antileukemic activity in patients with CML in whom treatment with interferon alfa had failed and demonstrates the potential for the development of anticancer drugs based on the specific molecular abnormality present in a human cancer.
Journal ArticleDOI
Cancer genes and the pathways they control.
TL;DR: The purposes of this review are to highlight examples of progress in many areas of cancer research, indicate where knowledge is scarce and point out fertile grounds for future investigation.
Journal ArticleDOI
Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia
Hagop M. Kantarjian,Charles L. Sawyers,Andreas Hochhaus,François Guilhot,Charles A. Schiffer,Carlo Gambacorti-Passerini,Dietger Niederwieser,Debra Resta,Renaud Capdeville,Ulrike Zoellner,Moshe Talpaz,Brian J. Druker +11 more
TL;DR: Imatinib induced high rates of cytogenetic and hematologic responses in patients with chronic-phase CML in whom previous interferon therapy had failed, and CML had not progressed to the accelerated or blast phases after a median follow-up of 18 months.
Journal ArticleDOI
Involvement of the bcl-2 gene in human follicular lymphoma
TL;DR: Chromosome 18-specific DNA probes for the areas flanking the breakpoints also detected RNA transcripts 6 kilobases in length in various cell types, and the gene coding for these transcript seems to be interrupted in most cases of follicular lymphomas carrying the t(14;18) chromosomal translocation.
Journal ArticleDOI
Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells
Riccardo Dalla-Favera,Marco Bregni,Jan Erikson,David A. Patterson,Robert C. Gallo,Carlo M. Croce +5 more
TL;DR: Using a DNA probe that is specific for the complete gene (c-myc), different somatic cell hybrids possessing varying numbers of human chromosomes were analyzed by the Southern blotting technique and results indicate that the human c- myc gene is located on chromosome 8.
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