High-Resolution Serum Proteomic Profiling of Alzheimer Disease Samples Reveals Disease-Specific, Carrier-Protein–Bound Mass Signatures

Lopez, Mary F.; Mikulskis, Alvydas; Kuzdzal, Scott; Bennett, David A.; Kelly, Jeremiah F.; Golenko, Eva; DiCesare, Joseph L.; Denoyer, E. R.; Patton, Wayne F.; Ediger, Richard; Sapp, Lisa; Ziegert, Tillmann; Lynch, Christopher J.; Kramer, Susan M.; Whiteley, Gordon; Wall, Michael R.; Mannion, David; Cioppa, Guy della; Rakitan, John S.; Wolfe, Gershon M.

doi:10.1373/clinchem.2005.053090

Cited by 131 publications

(87 citation statements)

References 25 publications

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“…Because proteins released from live or dying cancer cells are readily degraded or cleared from the serum, the degradation products of these proteins attract significant attention as peptide serum biomarkers (1). However, because small peptides are unstable in the serum, the search for disease-specific serum markers was redirected to peptides adsorbed to the "molecular sponge" serum albumin, known to carry with it a variety of peptides (2,3). "Immuno-MS" of serum albumin with its adsorbed peptides was thus proposed as a potentially promising alternative for separation of subsets of peptides from human sera for analysis by MAL-DI-MS (1,4,5).…”

mentioning

confidence: 99%

Soluble plasma HLA peptidome as a potential source for cancer biomarkers

Bassani-Sternberg

Barnea

Beer

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

120

133

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The HLA molecules are membrane-bound transporters that carry peptides from the cytoplasm to the cell surface for surveillance by circulating T lymphocytes. Although low levels of soluble HLA molecules (sHLA) are normally released into the blood, many types of tumor cells release larger amounts of these sHLA molecules, presumably to counter immune surveillance by T cells. Here we demonstrate that these sHLA molecules are still bound with their authentic peptide repertoires, similar to those of the membranal HLA molecules (mHLA). Therefore, a single immunoaffinity purification of the plasma sHLA molecules, starting with a few milliliters of patients' blood, allows for identification of very large sHLA peptidomes by mass spectrometry, forming a foundation for development of a simple and universal blood-based cancer diagnosis. The new methodology was validated using plasma and tumor cells of multiple-myeloma and leukemia patients, plasma of healthy controls, and with cultured cancer cells. The analyses identified thousands of sHLA peptides, including some cancer-related peptides, present among the sHLA peptidomes of the cancer patients. Furthermore, because the HLA peptides are the degradation products of the cellular proteins, this sHLA peptidomics approach opens the way for investigation of the patterns of protein synthesis and degradation within the tumor cells.

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mentioning

confidence: 99%

Soluble plasma HLA peptidome as a potential source for cancer biomarkers

Bassani-Sternberg

Barnea

Beer

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

120

133

View full text Add to dashboard Cite

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“…For example, with a QqTOF instrument, high mass proteins have been well detected in intact form [13]. Also, MALDI time-of-flight signals for Alzheimer biomarkers have been improved [14]. Efficient ion guides with inert or reactive gas are necessary and useful in collisioninduced dissociation (CID) and inductively coupled plasma (ICP) reaction cells [15,16].…”

Section: Ion Guiding and Collisional Focusingmentioning

confidence: 99%

Computer simulations of a new three rods ion optic (TRIPOLE) with high focusing and mass filtering capabilities

Salazar

Masujima

2007

J. Am. Soc. Mass Spectrom.

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A novel three rod (tripole) ion optic to which three AC voltages with symmetrically delayed phase shifts were applied to each electrode. We studied its ion guiding, focusing, and mass filtering capabilities by SIMION ver. 7.0 computer simulations. An electric field mathematical model was developed to calculate the pseudopotential of the tripole radial AC force. The tripole showed stable ion guiding for wide ranges of AC amplitude; better collisional focusing than hexapole and octapole and similar focusing as quadrupole (rod pole). Also, the ion optic clearly showed interesting mass filtering potential when the phase shift was asymmetrically delayed. The symmetric shape of the pseudopotential field explained the tripole ion guiding and focusing capabilities. For mass filtering, the pseudopotential was asymmetric and its effect was balanced with DC voltage to separate the ions, depending in their masses. The resolution was much lower than quadrupole but useful when rough filtering was required. (J Am Soc Mass Spectrom 2007, 18, 413-421)

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“…June Kinoshita: David Bennett and colleagues at Perkin Elmer also recently published an interesting proteomic study of AD biomarkers in serum [2].…”

Section: Jens Ecksteinmentioning

confidence: 99%