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|Alzheimer’s Disease and Neurological Disorders|Cellular Signaling|Cytokines|
|General Biomarkers and Toxicology Assays|Immunogenicity|Metabolic Assays|Methods & Technology|


General Biomarkers and Toxicology Assays

Enter author, analyte, or keyword to search publications.

Bragt, M.C., Mensink, R.P. (2011) Comparison of the effects of n-3 long chain polyunsaturated fatty acids and fenofibrate on markers of inflammation and vascular function, and on the serum lipoprotein profile in overweight and obese subjects. Nutr Metab Cardiovasc Dis. [Epub ahead of print].

TNFalpha, TNFa, TNF-a, TNF?, TNF-?, Tumor Necrosis Factor Receptor, TNFR1, TNFR2, Monocyte Chemotactic Protein, Intercellular Adhesion Molecule, ICAM1, Vascular Cell Adhesion Molecule, VCAM1



Analytes tested using MSD® assays: ICAM-1, MCP-1, VCAM-1, TNF-R1, TNF-R2
Matrix tested: Human plasma
Summary: In this study, the effects of n-3 long chain polyunsaturated fatty acids (n3-LCPUFA) and fenofibrate on a range of cardiovascular disease biomarkers were compared in overweight and obese individuals. Fenofibrate and n3-LCPUFA are both activators of PPARa, which in turn can lower serum triglycerides and increase HDL.
Brandon, D.L. (2011) Detection of Ricin Contamination in Ground Beef by Electrochemiluminescence Immunosorbent Assay. Toxins 2011, 3, 398-408.

Ricinus communis



Analytes tested using MSD assays: Ricin
Matrix tested: Ground beef homogenates
Summary: In this study, MSD platform was evaluated in different assay formats for the detection of ricin, a highly toxic protein, in a complex matrix such as ground beef.
Burkholder, T.P., Clayton, J.R., Rempala, M.E., Henry, J.R., Knobeloch, J.M., Mendel, D., McLean, J.A., Hao, Y., Barda, D.A., Considine, E.L., Uhlik, M.T., Chen, Y., Ma, L., Bloem, L.J., Akunda, J.K., McCann, D.J., Sanchez-Felix, M., Clawson, D.K., Lahn, M.M., Starling, J.J. (2011) Discovery of LY2457546: a multi-targeted anti-angiogenic kinase inhibitor with a novel spectrum of activity and exquisite potency in the acute myelogenous leukemia-Flt-3-internal tandem duplication mutant human tumor xenograft model. Invest New Drugs. 2011 Mar 1. [Epub ahead of print].

Ephrin receptor B4, Multikinase inhibitor, in vivo target inhibition, xenograft efficacy, sunitinib



Analytes tested using MSD assays: EphB4
Matrix tested: Cell lysates
Summary: This study evaluated a new compound called LY2457546, an inhibitor of multiple receptor tyrosine kinases (RTK), in terms of its potency, ability to inhibit several RTK pathways, pharmacokinetics, toxicity profile, and in vivo characteristics.
Capell, A., Liebscher, S., Fellerer, K., Brouwers, N., Willem, M., Lammich, S., Gijselinck, I., Bittner, T., Carlson, A.M., Sasse, F., Kunze, B., Steinmetz, H., Jansen, R., Dormann, D., Sleegers, K., Cruts, M., Herms, J., Van Broeckhoven, C., Haass, C. (2011) Rescue of progranulin deficiency associated with frontotemporal lobar degeneration by alkalizing reagents and inhibition of vacuolar ATPase. J Neurosci. Vol. 31(5):1885-94.
Analytes tested using MSD assays: Progranulin
Matrix tested: Human and mouse cell culture medium
Summary: The aim of this study was to evaluate multiple compounds that can stimulate the production and/or secretion of progranulin, a protein with neurotrophic properties. Haploinsufficiency and decreased levels of progranilin has been related to high risk of familial frontotemporal lobar degeneration (FTLD).
Giaccone, G., Rajan, A., Berman, A., Kelly, R.J., Szabo, E., Lopez-Chavez, A., Trepel, J., Lee, M.J., Cao, L., Espinoza-Delgado, I., Spittler, J., Loehrer, P.J. Sr. (2011) Phase II Study of Belinostat in Patients With Recurrent or Refractory Advanced Thymic Epithelial Tumors. J Clin Oncol. Vol. 29(15):2052-9. Epub 2011 Apr 18.

vascular endothelial growth factor receptor, placental growth factor, basic fibroblast growth factor



Analytes tested using MSD assays: VEGF, soluble VEGF-R1/Flt-1, bFGF, PlGF (MSD Human Growth Factor Panel I Kit)
Matrix tested: Human plasma
Summary: This paper provides the results of a phase II clinical study of belinostat—an inhibitor of histone deacetylase (HDAC)—in patients with thymic tumors.
Gupte, J., Yang, L., Wu, X., Weiszmann, J., Hecht, R., Lemon, B., Lindberg, R., Wang, Z., Li, Y. (2011) The FGFR D3 Domain Determines Receptor Selectivity For Fibroblast Growth Factor 21. J Mol Biol. [Epub ahead of print].
Analytes tested using MSD assays: Phospho ERK1/2
Matrix tested: Cell lysates
Summary: The aim of this study was to elucidate the beta-Klotho-dependent signaling mechanism of fibroblast growth factor 21 (FGF21) by determining the domains of FGF21 that confer receptor-specificity, interaction, and activation.
Ha, S., Ou, Y., Vlasak, J., Li, Y., Wang, S., Vo, K., Du, Y., Mach, A., Fang, Y., Zhang, N. (2011) Isolation and Characterization of IgG1 with Asymmetrical Fc Glycosylation. Glycobiology. 2011 Apr 5. [Epub ahead of print].

Asymmetrical glycosylation, Fc effector function, Fc-gamma-R binding



Analytes tested using MSD assays: Receptor phosphorylation
Matrix tested: Cell lysates
Summary: This study evaluated the effect of hemi-glycosylation of IgG on its thermal stability, functional activity, and Fc effector functions, and compared the results with that obtained from fully glycosylated IgG.
Kummar, S., Gutierrez, M.E., Chen, A., Turkbey, I.B., Allen, D., Horneffer, Y.R., Juwara, L., Cao, L., Yu, Y., Kim, Y.S., Trepel, J., Chen, H., Choyke, P., Melillo, G., Murgo, A.J., Collins, J., Doroshow, J.H. (2011) Phase I trial of vandetanib and bevacizumab evaluating the VEGF and EGF signal transduction pathways in adults with solid tumours and lymphomas. Eur J Cancer. Vol. 47(7):997-1005. Epub 2011 Jan 17.

vascular endothelial growth factor receptor, placental growth factor, basic fibroblast growth factor, epidermal growth factor



Analytes tested using MSD assays: VEGF, soluble VEGF-R1/Flt-1, bFGF, PlGF (MSD Human Growth Factor Panel I Kit)
Matrix tested: Human plasma
Summary: This paper is based on a phase I clinical study that evaluated the combinatorial effect of bevacizumab, an anti-VEGF antibody, and vandetanib, an investigational small molecule against VEGF-R2 and EGF.
Masson, C.J., Mensink, R.P. (2011) Exchanging Saturated Fatty Acids for (n-6) Polyunsaturated Fatty Acids in a Mixed Meal May Decrease Postprandial Lipemia and Markers of Inflammation and Endothelial Activity in Overweight Men. J Nutr. 2011 Mar 23. [Epub ahead of print].

Interleukin, IL6, IL8, tumor necrosis factor, TNFalpha, TNFa, TNF-a, TNF-?, TNF?, monocyte chemoattractant protein-1, Inter-Cellular Adhesion Molecule-1, vascular cell adhesion molecule-1, TNF-receptor



Analytes tested using MSD assays: IL-6, IL-8, TNF-alpha, TNF-RI, TNF-RII, MCP-1, soluble ICAM-1, soluble VCAM-1
Matrix tested: Human plasma and serum
Summary: This study investigated the effects of different types of fat on markers of postprandial inflammation and endothelial activation in overweight men who have a high risk for developing metabolic syndrome.
McDaniel, J.C., Massey, K., Nicolaou, A. (2011) Fish oil supplementation alters levels of lipid mediators of inflammation in microenvironment of acute human wounds. Wound Repair Regen. Vol. 19(2):189-200.
Analytes tested using MSD assays: Myeloperoxidase (MPO)
Matrix tested: Human wound blister fluid
Summary: This study investigated whether oral administration of polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) would affect lipid mediators in acute wound environments and reduce inflammation and polymorphonuclear leukocyte recruitment.
McElrath, T.F., Fichorova, R.N., Allred, E.N., Hecht, J.L., Ismail, M.A., Yuan, H., Leviton, A; ELGAN Study Investigators. (2011) Blood protein profiles of infants born before 28th weeks differ by pregnancy complication. Am J Obstet Gynecol. [Epub ahead of print].

C-Reactive Protein, serum amyloid A, myeloperoxidase, Interleukin, IL-1b, IL1b, IL1beta, IL-1ß, IL1ß, IL6, IL8, Interleukin-6 Receptor, tumor necrosis factor, TNFalpha, TNFa, TNF-a, TNF?, TNF-?, Tumor Necrosis Factor Receptor, TNFR1, TNFR2, Monocyte Chemotactic Protein, Macrophage Inflammatory Protein, MIP-1b, MIP1b, Regulated upon Activation, Normal T-cell Expressed, and Secreted, Intercellular Adhesion Molecule, ICAM1, ICAM3, Vascular Cell Adhesion Molecule, Matrix Metalloproteinase, Vascular Endothelial Growth Factor Receptor, KDR, Flt-1, Insulin Growth Factor Binding Protein-1, Interferon-inducible T cell Alpha-Chemoattractant



Analytes tested using MSD assays: CRP, SAA, MPO, IL-1beta, IL-6, IL-6R, TNF-alpha, TNF-R1, TNF-R2, IL-8, MCP-1, MCP-4, MIP-1beta, RANTES, IGFBP-1, ITAC, ICAM-1, ICAM-3, E-selectin, VCAM-1, MMP-1, MMP-9, VEGF, VEGF-R1, VEGF-R2
Matrix tested: Elution from dried blood spots
Summary: In this study, a range of 25 biomarkers was measured in the blood of 798 infants born before the 28th week of gestation in order to correlate their levels with the disorder that led to preterm delivery.
Ren, D., Darlucio, M.R., Chou, J.H. (2011) Development of a multi-product leached protein A assay for bioprocess samples containing recombinant human monoclonal antibodies. J Immunol Methods. Vol. 366(1-2):20-7.

bioprocess



Analytes tested using MSD assays: Protein A
Matrix tested: Assay diluent
Summary: In this study, a novel assay was developed on the MSD platform to determine the levels of protein A contamination during monoclonal antibody purification process. Acid dissociation was used to dissociate the IgG-protein A complex, followed by neutralization step. The authors noted the robustness, high sensitivity and efficiency of this assay for protein A determination.
Xie, R., Chung, J.Y., Ylaya, K., Williams, R.L., Guerrero, N., Nakatsuka, N., Badie, C., Hewitt, S.M. (2011) Factors influencing the degradation of archival formalin-fixed paraffin-embedded tissue sections. J Histochem Cytochem. Vol. 59(4):356-65.

Antigenicity, immunohistochemistry, protein array, tissue processing, FFPE



Analytes tested using MSD assays: GAPDH
Matrix tested: Protein extracted from formalin-fixed paraffin-embedded (FFPE) tissue
Summary: The aim of this study was to analyze the effect of residual water in FFPE tissues, either due to inadequate tissue processing or the presence of humidity during storage, on protein integrity and antigenicity.
Bass, M.B., Sherman, S.I., Schlumberger, M.J., Davis, M.T., Kivman, L., Khoo, H.M., Notari, K.H., Peach, M., Hei, Y.J., Patterson, S.D. (2010) Biomarkers as Predictors of Response to Treatment with Motesanib in Patients with Progressive Advanced Thyroid Cancer. J Clin Endocrinol Metab. Vol. 95(11):5018-27.

Vascular Endothelial Growth Factor Receptor, KDR, Flt-1



Analytes tested using MSD assays: Soluble VEGF-R1, PlGF (placental growth factor), bFGF (basic fibroblast growth factor), VEGF (MSD Human Growth Factor Panel 1), soluble Kit (sKit), soluble VEGFR2 (MSD Human Growth Factor Panel 2)
Matrix tested: Human serum and plasma
Summary: This study examined the effects of motesanib administration on the levels of biomarkers associated with tumor response and progression free survival in patients with advanced medullary (MTC) and differentiated thyroid cancers (DTC).
Betts, A.M., Clark, T.H., Yang, J., Treadway, J.L., Li, M., Giovanelli, M.A., Abdiche, Y., Stone, D.M., Paralkar, V.M. (2010) The application of target information and preclinical pharmacokinetic/pharmacodynamic modeling in predicting clinical doses of a Dickkopf-1 antibody for osteoporosis. J Pharmacol Exp Ther. Vol. 333(1):2-13.

Interleukin, IL1b, IL-1b, IL1beta, IL-1ß, IL1ß, IL6, IL8, TGF, matrix metalloproteinase, Macrophage inflammatory protein 3beta, Growth regulated oncogene alpha, Tumour necrosis factor related weak inducer of apoptosis, Neutrophil gelatinase associated lipocalin, OPG, Vascular endothelial growth factor, Brain derived neurotrophic factor, Metalloproteinase-9, Tissue inhibitor of metalloproteinase-1



Analytes tested using MSD assays: Brain derived neurotrophic factor, GRO-alpha, IL-1beta, MIP-3beta, MMP-9, NGAL, Osteoprotegerin, VEGF, TIMP-1, TWEAK
Matrix tested: Rat serum
Summary: This study investigated individual sensitivity, associated biomarkers and hypothesized mechanisms of placebo response in a randomized clinical trial for irritable bowel syndrome. This was done by investigating the biological changes of serum markers over time in patients that self-report improvements in their symptoms.
Bennuru, S., Maldarelli, G., Kumaraswami, V., Klion, A.D., Nutman, T.B. (2010) Elevated levels of plasma angiogenic factors are associated with human lymphatic filarial infections. Am J Trop Med Hyg. Vol. 83(4):884-90.

vascular endothelial growth factor receptor, placental growth factor, basic fibroblast growth factor, angiopoietin, Ang1, Ang2



Analytes tested using MSD assays: VEGF-A, soluble VEGF-R1, bFGF, PlGF (MSD Human Growth Factor I Kit), VEGF-C, VEGF-D, Ang-1, Ang-2
Matrix tested: Human plasma
Summary: The aim of this study was to determine whether filarial infections are associated with an increase in pro-angiogenic factors such as Ang-1 and Ang-2, which drive lymphatic endothelial cell (LEC) activation, proliferation and remodeling.
Brave, S.R., Eberlein, C., Shibuya, M., Wedge, S.R., Barry, S.T. (2010) Placental growth factor neutralising antibodies give limited anti-angiogenic effects in an in vitro organotypic angiogenesis model. Angiogenesis. Vol. 13(4):337-47.

VEGF, PlGF, VEGFR-1, Flt-1, VEGFR-2, KDR, Angiogenesis, Endothelial cells, vascular endothelial growth factor receptor



Analytes tested using MSD assays: Phosphorylated VEGFR-1
Matrix tested: Cell lysates
Summary: This study investigated the role of placental growth factor and the VEGF family ligands in endothelial cell proliferation, migration and differentiation into tubes as related to angiogenesis.
Chao, C.C., Chen, S.J., Adamopoulos, I.E., Judo, M., Asio, A., Ayanoglu, G., Bowman, E.P. (2010) Structural, cellular, and molecular evaluation of bone erosion in experimental models of rheumatoid arthritis: Assessment by µCT, histology, and serum biomarkers. Autoimmunity. 2010 Apr 12. [Epub ahead of print].

Micro-computed tomography, arthritis, anti-IL-17



Analytes tested using MSD assays: RANKL
Matrix tested: Mouse serum
Summary: This paper investigated the structural, cellular, and molecular aspects of inflammation-driven bone resorption process in rodent models of arthritis. Structural micro-computed tomography, cellular histology and serum biomarker analysis were done to evaluate bone erosion.
Cramer, D.W., Vitonis, A.F., Pinheiro, S.P., McKolanis, J.R., Fichorova, R.N., Brown, K.E., Hatchette, T.F., Finn, O.J. (2010) Mumps and ovarian cancer: modern interpretation of an historic association. Cancer Causes Control. Vol. 21(8):1193-201. Epub 2010 Jun 18.

ovarian cancer, mumps parotitis



Analytes tested using MSD assays: Cancer Antigen 125 (CA125), MUC1
Matrix tested: Human serum
Summary: This study tested whether abnormal expression of MUC-1 antibodies in the inflamed parotid gland during mumps infection provides immunity against ovarian cancer. MUC1 is a cancer-associated antigen.
French, K.J., Coatney, R.W., Renninger, J.P., Hu, C.X., Gales, T.L., Zhao, S., Storck, L.M., Davis, C.B., McSurdy-Freed, J., Chen, E., Frazier, K.S. (2010) Differences in effects on myocardium and mitochondria by angiogenic inhibitors suggest separate mechanisms of cardiotoxicity. Toxicol Pathol. Vol. 38(5):691-702.

angiogenesis, pazopanib, sunitinib, sorafenib, cardiotoxicity, kinase inhibitor



Analytes tested using MSD assays: Cardiac troponin I (cTnI)
Matrix tested: Rat plasma
Summary: This study tested the hypothesis whether cardiotoxicity is an effect of angiogenic inhibitors by testing the effects of pazopanib, sunitinib and sorafenib in a rat dobutamine-induced cardiac stress model and a rat cardiomyocyte in vitro model.
Fujisaka, Y., Yamada, Y., Yamamoto, N., Shimizu, T., Fujiwara, Y., Yamada, K., Tamura, T., Watanabe, H., Sun, Y.N., Bass, M.B., Seki, M. (2010) Phase 1 study of the investigational, oral angiogenesis inhibitor motesanib in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2010 Jan 28. [Epub ahead of print].

Motesanib, Maximum tolerated dose, cKit, Flt 1, VEGFR



Analytes tested using MSD assays: PlGF (placental growth factor), bFGF (basic fibroblast growth factor), VEGF (Vascular endothelial growth factor receptor), sKDR (soluble KDR), Flt-1 (fms-related tyrosine kinase 1), soluble c-Kit
Matrix tested: Human serum
Summary: This paper provides the results of a phase I clinical trial which examined the safety and pharmacokinetics of an antagonist of VEGF receptors 1, 2 and 3, platelet-derived growth factor receptor, and c-Kit patients with advanced solid tumors.
Gooding, K.M., Tooke, J.E., von Lany, H., Mitra, M., Ling, R., Ball, C.I., Mawson, D., Skinner, K., Shore, A.C. (2010) Capillary pressure may predict preclinical changes in the eye. Diabetologia. 2010 Jun 6. [Epub ahead of print].

obesity, diabetic retinopathy



Analytes tested using MSD assays: C-reactive protein (CRP)
Matrix tested: Human plasma
Summary: This study examined the mechanisms underlying macular thickness in non-diabetic individuals, in particular the variables controlling fluid movement across the blood vessel wall, such as capillary pressure and microvascular filtration capacity (Kf).
Kim, C.X., Bailey, K.R., Klee, G.G., Ellington, A.A., Liu, G., Mosley, T.H. Jr, Rehman, H., Kullo, I.J. (2010) Sex and ethnic differences in 47 candidate proteomic markers of cardiovascular disease: the mayo clinic proteomic markers of arteriosclerosis study. Cancer Chemother Pharmacol. 2010 Jan 28.

CVD



Analytes tested using MSD assays: Osteopontin (OPN), Osteoprotegerin (OPG), Osteonectin (ONN), Osteocalcin (OCN)
Matrix tested: Human serum and plasma
Summary: This study investigated multimarker approaches for early detection of cardiovascular disease by measuring the differences in circulating levels of 47 protein markers, suggested to play a role in arteriosclerosis and hypertension, in stored blood samples of 2561 participants.
Kokkotou, E., Conboy, L.A., Ziogas, D.C., Quilty, M.T., Kelley, J.M., Davis, R.B., Lembo, A.J., Kaptchuk, T.J. (2010) Serum correlates of the placebo effect in irritable bowel syndrome. Neurogastroenterol Motil. Vol. 22(3):285-e81.

Interleukin, IL1b, IL-1b, IL1beta, IL-1ß, IL1ß, IL6, IL8, TGF, matrix metalloproteinase, Macrophage inflammatory protein 3beta, Growth regulated oncogene alpha, Tumour necrosis factor related weak inducer of apoptosis, Neutrophil gelatinase associated lipocalin, OPG, Vascular endothelial growth factor, Brain derived neurotrophic factor, Metalloproteinase-9, Tissue inhibitor of metalloproteinase-1



Analytes tested using MSD assays: Brain derived neurotrophic factor, GRO-alpha, IL-1beta, MIP-3beta, MMP-9, NGAL, Osteoprotegerin, VEGF, TIMP-1, TWEAK
Matrix tested: Human serum
Summary: This study investigated individual sensitivity, associated biomarkers and hypothesized mechanisms of placebo response in a randomized clinical trial for irritable bowel syndrome. This was done by investigating the biological changes of serum markers over time in patients that self-report improvements in their symptoms.
Luo, J., Wu, S.J., Lacy, E.R., Orlovsky, Y., Baker, A., Teplyakov, A., Obmolova, G., Heavner, G.A., Richter, H.T., Benson, J. (2010) Structural basis for the dual recognition of IL-12 and IL-23 by ustekinumab. J Mol Biol. Vol. 402(5):797-812. Epub 2010 Aug 4.

Interleukin, IL12, IL23, IL23p40, IL-23p40, autoimmune disease, psoriasis, cytokine–antibody complex



Analytes tested using MSD assays: IL-12 and IL-23 binding to Ustekinumab
Matrix tested: Assay buffer
Summary: The focus of this study was to determine the therapeutic mechanism of action of ustekinumab, a monoclonal antibody that neutralizes human IL-12 and IL-23 activity, by understanding the specificity of ustekinumab/target interaction, epitope characterization and stoichiometry analysis.
Mathialagan, S., Poda, G.I., Kurumbail, R.G., Selnessa, S.R., Halla, T., Reitza, B.A., Weinberg, R.A., Kishore, N., Mbalaviele, G. (2010) Expression, purification and functional characterization of IkB kinase-2 (IKK-2) mutants. Protein Expr Purif. Vol. 72(2):254-61.

Nuclear factor kappa B, NF kappa B, NFkB



Analytes tested using MSD assays: User developed assay for IKK-2 kinase activity
Matrix tested: Assay buffer
Summary: In this study, the authors conducted extensive site-directed mutagenesis and computational modeling to generate IKK-2 mutants in order to elucidate the structure–function relationship of IKK-2 inhibitors and enable the further design of IKK-2 inhibitors based on their structure.
Mishra, R., Grzybek, M., Niki, T., Hirashima, M., Simons, K. (2010) Galectin-9 trafficking regulates apical-basal polarity in Madin-Darby canine kidney epithelial cells. Proc Natl Acad Sci U S A. Vol. 107(41):17633-8. Epub 2010 Sep 22.

ciliogenesis, epithelial polarity, Forssman glycosphingolipid, raft clustering



Analytes tested using MSD assays: Receptor - ligand binding assays for Galectin-9
Matrix tested: Cell lysates, assay buffer
Summary: The aim of this study was to elucidate the role of galectins, specifically Galectin-9, in membrane trafficking processes and to identify the molecular steps involved in the transport machinery.
Ozer, J.S., Chetty, R., Kenna, G., Koppiker, N., Karamjeet, P., Li, D., Palandra, J., Lanevschi, A., Souberbielle, B.E., Ramaiah, S. (2010) Recommendations to qualify biomarker candidates of drug-induced liver injury. Biomark Med. Vol. 4(3):475-83.

GST-a, GST-a, GSTa, GSTa, alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase



Analytes tested using MSD assays: GST-alpha
Matrix tested: Mouse serum
Summary: This article provides a review on identifying novel biomarkers that can be used in combination with aminotransferases to specifically detect drug-induced liver injury.
Pang, S., Ahsan, E.S., Foy, C.A. (2010) Improved detection of cell surface proteins using an electrochemiluminescent cell-binding assay. J Immunol Methods. Vol. 362(1-2):176-9.
Analytes tested using MSD assays: User built assay for measuring cell surface protein (CD13) on HFF cells
Matrix tested: Cells from culture
Summary: MSD assay was used to detect CD13 on HFF cells in 96-and 384-well format with less than 100 cells/well. The focus of the study was to reduce the cell consumption for cell surface protein analysis, which is a distinct advantage of the MSD platform.
Piters E, Culha C, Moester M, Van Bezooijen R, Adriaensen D, Mueller T, Weidauer S, Jennes K, de Freitas F, Lowik C, Timmermans JP, Van Hul W, Papapoulos S. (2010) First missense mutation in the SOST gene causing sclerosteosis by loss of sclerostin function. Hum Mutat. Vol. 31(7):E1526-43.

SOST, Wnt, sclerosteosis



Analytes tested using MSD assays: Sclerostin
Matrix tested: HEK293T and Saos-2 cell culture medium and lysates
Summary: This study is based on genetic analysis of a patient with sclerostosis which lead to the identification of the first missense mutation in the SOST gene resulting in complete loss of function of sclerostin.
Rouse, R.L., Zhang, J., Stewart, S.R., Rosenzweig, B.A., Espandiari, P., Sadrieh, N.K. (2010) Comparative profile of commercially available urinary biomarkers in preclinical drug-induced kidney injury and recovery in rats. Kidney Int. [Epub ahead of print].

Glutathione S-transferases, renal papillary antigen, kidney injury molecule, neutrophil gelatinase-associated lipocalin



Analytes tested using MSD assays:
  1. Kidney Injury Panel I (Albumin, KIM-1, Osteopontin, Lipocalin-2/NGAL)
  2. Argutus AKI Test® (RPA-1, alpha-GST, GSTYb1)
  3. Clusterin
Matrix tested: Rat urine
Summary: In this study, the MSD platform was used to evaluate comparative injury response and obtain reversibility data for eight candidate biomarkers of kidney injury in rats that were administered with the nephrotoxin, gentamicin.
Serra, M., Papakonstantinou, S., Adamcova, M., O'Brien, P.J. (2010) Veterinary and toxicological applications for the detection of cardiac injury using cardiac troponin. The Veterinary Journal. Vol. 185(1): 50-57.

cardiac troponin I, cardiac troponin T, Fatty acid binding protein 3



Analytes tested using MSD assays: cTnI, cTnT, FABP3
Matrix tested: Animal plasma and serum
Summary: The aim of this study was to evaluate the diagnostic potential of cardiac Troponin as a biomarker of myocardial injury across multiple species (cattle, cats, dogs, horses, rabbits and rats) using six different immunoassays.
Sourial, S., Searchfield, L., Schuppe-Koistinen, I., Betton, G.R., Riccardi, D., Price, S.A. (2010) Application of Dolichos biflorus in immunoassay detection of kidney collecting duct biomarkers. Biomarkers. Vol. 15(5):424-35.

Renal papillary antigen 1, aquaporin 2, renal papillary necrosis



Analytes tested using MSD assays: Markers for renal toxicity
Matrix tested: Rat kidney extract, human kidney extract, rat urine, human urine
Summary: This paper is based on the development of MSD immunoassays to detect markers of collecting duct damage in rat and human samples. A lectin has been used together with an antibody for these assays, which circumvents the necessity for two antibodies for the same protein as this can be an issue for antigens with unknown molecular identity.
Sturm, B., Helminger, M., Steinkellner, H., Heidari, M.M., Goldenberg, H., Scheiber-Mojdehkar, B. (2010) Carbamylated erythropoietin increases frataxin independent from the erythropoietin receptor. Eur J Clin Invest. 2010 Apr 28. [Epub ahead of print].

Carbamylated erythropoietin, erythropoietin receptor, Friedreich's ataxia, human erythropoietin



Analytes tested using MSD assays: User developed assay for Frataxin
Matrix tested: Cell lysates
Summary: Previous studies have indicated that recombinant human erythropoietin (rhuEPO) significantly increases frataxin-expression in Friedreich's ataxia patients. This paper investigated the importance of erythropoietin receptor (EPO-R) as well as the effect of a recently developed EPO derivative called CEPO (carbamylated erythropoietin) for the frataxin increasing effect of recombinant human EPO.
Tailor, T.D., Hanna, G., Yarmolenko, P.S., Dreher, M.R., Betof, A.S., Nixon, A.B., Spasojevic, I., Dewhirst, M.W. (2010) Effect of pazopanib on tumor microenvironment and liposome delivery. Mol Cancer Ther. Vol. 9(6):1798-808.

Platelet derived growth factor receptor, vascular endothelial growth factor receptor, VEGFR-1, VEGFR-2, VEGFR-3, PDGFRalpha, PDGFRbeta, PDGFRa, PDGFRb, PDGFR-a, PDGFR-b, PDGFR-a, PDGFR-ß



Analytes tested using MSD assays: Total VEGFR-2, total PDGFR-ß
Matrix tested: NSCLC Tumor xenograft lysates
Summary: This study examined the role of pazopanib, a small molecule inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR-alpha and PDGFR-beta, on tumor interstitial fluid pressure (IFP), angiogenesis, hypoxia and liposomal drug delivery.
Thway, T., Macaraeg, C., Calamba, D., Patel, V., Tsoi, J., Ma, M., Lee, J., Desilva, B. (2010) Applications of a planar electrochemiluminescence platform to support regulated studies of macromolecules: Benefits and limitations in assay range. J Pharm Biomed Anal. Vol. 51(3):626-32.

Urinary biomarkers, Glomerular injury, Renal tubular injury, Cisplatin, Puromycin aminonucleoside, GST-a, GST-a, GSTa, GSTa, GST-µ, GST-mu, GSTµ, GSTmu, Kidney injury panel, Argutus AKI test®, kidney injury molecule 1, neutrophil gelatinase associated lipocalin



Analytes tested using MSD assays: KIM-1, NGAL, GST-alpha and GST-mu
Matrix tested: Rat plasma and urine
Summary: This study examined twelve different urinary nephrotoxic biomarkers in a rat renal tubular injury model induced by cisplatin (CDDP) and a glomerular injury model induced by puromycin aminonucleoside (PAN). The accuracy and sensitivity of these biomarkers for the detection of nephrotoxicity were analyzed by receiver operating characteristic (ROC) curve analysis.
Tonomura, Y., Tsuchiya, N., Torii, M., Uehara, T. (2010) Evaluation of the usefulness of urinary biomarkers for nephrotoxicity in rats. Toxicology. Vol. 273(1-3):53-9.

Keywords: automated liquid handler, Glutathione S-transferases, kidney injury molecule, neutrophil gelatinase-associated lipocalin



Analytes tested using MSD assays:
  1. Kidney Injury Panel I (KIM-1, Lipocalin-2/NGAL)
  2. Argutus AKI Test® (alpha-GST, GSTYb1)
Matrix tested: Rat urine
Summary: In this study, several urinary proteins were evaluated for their usefulness as biomarkers of renal tubular injury induced by cisplatin and glomerular injury induced by puromycin aminonucleoside. The levels of the biomarkers were tested at an early sampling point and at different time points.
Wice, B.M., Wang, S., Crimmins, D.L., Diggs-Andrews, K.A., Althage, M.C., Ford, E.L., Tran, H., Ohlendorf, M., Griest, T.A., Wang, Q., Fisher, S.J., Ladenson, J.H., Polonsky, K.S. (2010) -25 potentiates glucose-dependent insulinotropic polypeptide action via a novel cholinergic relay mechanism. J Biol Chem. Vol. 285(26):19842-53. Epub 2010 Apr 26.

GLP-1, GIP, type 2 diabetes mellitus



Analytes tested using MSD assays: User developed assay for Xenin-25 peptide on MSD bare plates
Matrix tested: Mouse plasma
Summary: In this study, the effect of xenin-25, a peptide reportedly produced by intestinal K cells, on the insulin secretory response to GIP (glucose-dependent insulinotropic polypeptide) has been tested in vivo. Effects were studied in two mouse models in which the response to GIP is blunted.
Wilson, D.C., Marinov, A.D., Blair, H.C., Bushnell, D.S., Thompson, S.D., Chaly, Y., Hirsch, R. (2010) Follistatin-like protein 1 is a mesenchyme-derived inflammatory protein and may represent a biomarker for systemic-onset juvenile rheumatoid arthritis. Arthritis Rheum. Vol. 62(8):2510-6.

Analytes tested using MSD assays: Follistatin like protein 1 (FSTL-1)
Matrix tested: Human serum and synovial fluid
Summary: The aim of this study was to elucidate the role of a novel proinflammatory molecule, FSLT-1, and the factors that induce its expression in arthritis, and to examine whether FSLT-1 overexpression occurs in cases of juvenile rheumatoid arthritis (JRA).
Witt, K.L., Malarkey, D.E., Hobbs, C.A., Davis, J.P., Kissling, G.E., Caspary, W., Travlos, G., Recio, L. (2010) No increases in biomarkers of genetic damage or pathological changes in heart and brain tissues in male rats administered methylphenidate hydrochloride (Ritalin) for 28 days. Environ Mol Mutagen. Vol. 51(1):80-8.

TnT, TnI, FABP3



Analytes tested using MSD assays: Troponin I, Troponin T, Fatty Acid Binding Protein (Cardiac Injury Panel 2)
Matrix tested: Rat serum
Summary: In this study, Wistar Han rats were treated with different levels of methylphenidate drug to test whether DNA damage is a possible complication of such a treatment. Methylphenidate is a commonly prescribed medication for attention deficit hyperactivity disorder (ADHD).
Yoon, S.S., Duda, D.G., Karl, D.L., Kim, T.M., Kambadakone, A.R., Chen, Y.L., Rothrock, C., Rosenberg, A.E., Nielsen, G.P., Kirsch, D.G., Choy, E., Harmon, D.C., Hornicek, F.J., Dreyfuss, J., Ancukiewicz, M., Sahani, D.V., Park, P.J., Jain, R.K., Delaney, T.F. (2010) Phase II Study of Neoadjuvant Bevacizumab and Radiotherapy for Resectable Soft Tissue Sarcomas. Int J Radiat Oncol Biol Phys. 2010 Oct 5. [Epub ahead of print].

vascular endothelial growth factor receptor, Sarcoma, angiogenesis inhibitors, radiotherapy, bevacizumab, biomarkers, interleukin, IL6, IL8, tumor necrosis factor, TNFa, TNGalpha, TNF-a, TNF-a, TNFa, clinical trial



Analytes tested using MSD assays: VEGF, soluble VEGFR-1, PlGF (placental growth factor), bFGF (basic fibroblast growth factor), IL-6, IL-8, TNF-alpha
Matrix tested: Human plasma
Summary: This paper provides the results of a clinical study testing the safety and efficacy of a combination of an angiogenesis inhibitor, bevacizumab along with radiotherapy in patients with soft tissue sarcomas.
Bruey, J.M., Kantarjian, H., Estrov, Z., Zhang, Z., Ma, W., Albitar, F., Abdool, A., Thomas, D., Yeh, C., O'Brien, S., Albitar, M. (2009) Circulating Ki-67 protein in plasma as a biomarker and prognostic indicator of acute lymphoblastic leukemia. Leuk Res. Vol. 34(2):173-6.

Acute lymphoblast leukemia, ECL



Analytes tested using MSD assays: User developed assay for Ki-67, a marker of cellular proliferation
Matrix tested: Human plasma
Summary: In this study, the authors developed an electrochemiluminescence-based immunoassay to explore the prognostic relevance of circulating Ki-67 in plasma in individuals with hematologic disease, using acute lymphoblast leukemia as a model.
Cheng, L.W., Stanker, L.H., Henderson, T.D. 2nd, Lou, J., Marks, J.D. (2009) Antibody protection against botulinum neurotoxin intoxication in mice. Infect Immun. Vol. 77(10):4305-13.

botulism, BoNT/A, BoNT/B, F1-2, F1-40



Analytes tested using MSD assays: Botulinum neurotoxin serotype A
Matrix tested: Mouse serum
Summary: In this study, the ability of monoclonal antibodies to neutralize botulinum toxin serotype A (BoNT/A) was examined in systemic and oral mouse models of botulism.
Cho, C.Y., Keener, W.K., Garber, E.A. (2009) Application of deadenylase electrochemiluminescence assay for ricin to foods in a plate format. J Food Prot. Vol. 72(4):903-6.
Analytes tested using MSD assays: User developed deadenylase assay to measure ricin using MSD Streptavidin plates
Matrix tested: Fruit and vegetable juices
Summary: This study is based on the development of an ECL assay to measure ricin activity in juices on the MSD platform and comparing it with an existing bead based assay. The plate based MSD assay showed better signal / noise ratio and was less sensitive to matrix effects.
Francone, O.L., Tu, M., Royer, L.J., Zhu, J., Stevens, K., Oleynek, J.J., Lin, Z., Shelley, L., Sand, T., Luo, Y., Kane, C.D. (2009) The hydrophobic tunnel present in LOX-1 is essential for oxidized Low-density lipoprotein recognition and binding. J Lipid Res. Vol. 50(3):546-55.

low density lipoprotein, LDL, LDL-oxidation, scavenger receptors



Analytes tested using MSD assays: User developed assay for oxidized LDL / LOX-1 receptor complex
Matrix tested: Assay buffer
Summary: The aim of this study was to identify the functional domains responsible for the binding of oxidized-LDL to the LOX-1 receptor using a series of site-directed mutants that were designed through computer modeling and X-ray crystallography.
Kumar, K.G., Sutton, G.M., Dong, J.Z., Roubert, P., Plas, P., Halem, H.A., Culler, M.D., Yang, H., Dixit, V.D., Butler, A.A. (2009) Analysis of the therapeutic functions of novel melanocortin receptor agonists in MC3R- and MC4R-deficient C57BL/6J mice. Peptides. Vol. 30(10):1892-900.

cAMP, DIO, Obesity, Diabetes, Insulin, Melanocortins, Proopiomelanocortin, Melanocyte-stimulating hormones



Analytes tested using MSD assays: Cyclic AMP
Matrix tested: Cell lysates
Summary: This study examined the effects of novel melanocortin receptor agonists which efficiently reduces food intake, body weight and reverse some aspects of the metabolic syndrome when administered peripherally to diet induced obese mice.
Liang, S., Connell, G.J. (2009) An electrochemiluminescent aptamer switch for a high-throughput assay of an RNA editing reaction. RNA. Vol. 15(10):1929-38.

electrochemiluminescence, Trypanosoma, Lieshmania



Analytes tested using MSD assays: Edited RNA species
Matrix tested: Assay buffer
Summary: In this study, a novel ECL based assay was developed on the MSD platform for the detection of edited RNA in the low femtomole range in a high-throughput format. ECL signal is generated by a conformational change in the RNA induced by the editing.
Migone, T.S., Subramanian, G.M., Zhong, J., Healey, L.M., Corey, A., Devalaraja, M., Lo, L., Ullrich, S., Zimmerman, J., Chen, A., Lewis, M., Meister, G., Gillum, K., Sanford, D., Mott, J., Bolmer, S.D. (2009) Raxibacumab for the Treatment of Inhalational Anthrax. The New England Journal of Medicine. Vol. 361(2):135-144.
Analytes tested using MSD assays: Bacillus anthracis protective antigen
Matrix tested: Rabbit serum, Cynomolgus monkey serum
Summary: This paper provides the results of a randomized, placebo-controlled study in two different animal models of anthrax to assess the efficacy of raxibacumab drug administered as a prophylactic agent and after the onset of systemic disease.
Ohya, T., Miaczynska, M., Coskun, U., Lommer, B., Runge, A., Drechsel, D., Kalaidzidis, Y., Zerial, M. (2009) Reconstitution of Rab- and SNARE-dependent membrane fusion by synthetic endosomes. Nature. Vol. 459(7250):1091-7.

GTPase, intracellular transport, proteoliposome



Analytes tested using MSD assays: Ligand binding assays
Matrix tested: Assay buffer
Summary: In this study, the authors successfully performed an in vitro reconstitution of the intracellular membrane fusion machinery, by using 17 different purified proteins and liposomes, to determine the minimal protein and lipid requirement for endosome fusion. The authors highlighted that the MSD platform provides high sensitivity and dynamic range, as well as minimal background signals.
Ray, C.A., Patel, V., Shih, J., Macaraeg, C., Wu, Y., Thway, T., Ma, M., Lee, J.W., Desilva, B. (2009) Application of multi-factorial design of experiments to successfully optimize immunoassays for robust measurements of therapeutic proteins. J Pharm Biomed Anal. Vol. 49(2):311-8.

Tecan Evo pipettor, ELISA



Matrix tested: Cynomolgus monkey serum, human serum
Summary: In this paper, the authors describe a multi-factorial design of experiments (DOE) method as a tool for optimizing bridging immunoassays in therapeutic drug measurement and in immunogenicity assessment.
Schoenhoff, F.S, Fu, Q., Van Eyk, J.E. (2009) Cardiovascular proteomics: implications for clinical applications. Clin Lab Med. Vol. 29(1):87-99.

vascular injury panel, CRP, ICAM, VCAM, SAA, multiplex, Bio-Plex



Summary: This article reviews the proteomics techniques with regard to biomarker discovery, validation and verification and discusses the advantages and shortfalls involved in taking proteomics from bench to a clinical setting. MSD technology has been highlighted for its minimal maintenance and robustness.
Sun, D., Hamlin, D., Butterfield, A., Watson, D.E., Smith, H.W. (2009) Electrochemiluminescent immunoassay for rat skeletal troponin I (Tnni2) in serum. J Pharmacol Toxicol Methods. Vol. 61(1):52-8.

cardiac Troponin I, cTnI, monomeric



Analytes tested using MSD assays: Skeletal Troponin I (sTnI)
Matrix tested: Rat serum
Summary: This study is based on the use of MSD technology to develop a sensitive assay that can reliably detect sTnI with minimal cross-reactivity to cTnI in rat serum under reducing conditions. MSD has been highlighted for its dynamic range and the ability for multiplexing.
Tonomura, Y., Mori, Y., Torii, M., Uehara, T. (2009) Evaluation of the usefulness of biomarkers for cardiac and skeletal myotoxicity in rats. Toxicology. Vol. 266(1-3):48-54.

cardiotoxicity, skeletal myotoxocity, acetylcholinesterase, carbofuran, fatty acid binding protein 3 (Fabp3), myosin light chain 1 (MLC1), cardiac troponin I (cTnI), cardiac troponin T (cTnT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK)



Analytes tested using MSD assays: Cardiac injury panel 1 (MLC3, Fabp3, cTnI, cTnT)
Matrix tested: Rat serum
Summary: In this study, the authors utilized receiver operating characteristics (ROC) curve analysis to quantitate the relative usefulness of several cardiac and skeletal biomarkers of myotoxicity using two rat models.
Zarrinkar, P.P., Gunawardane, R.N., Cramer, M.D., Gardner, M.F., Brigham, D., Belli, B., Karaman, M.W., Pratz, K.W., Pallares, G., Chao, Q., Sprankle, K.G., Patel, H.K., Levis, M., Armstrong, R.C., James, J., Bhagwat, S.S. (2009) AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood. Vol. 114(14):2984-2992.

Sunitinib, sorafenib



Analytes tested using MSD assays: User developed assay for Phospho and Total FLT3
Matrix tested: Lysates from MV4-11 and RS4;11 cells, Tumor xenograft lysates, PBMC lysates
Summary: This paper is based on the comparison of a second generation FLT3 inhibitor (therapy for acute myeloid leukemia) with the first generation candidates in terms of potency, selectivity and pharmacokinetics.
Azad, N.S., Posadas, E.M., Kwitkowski, V.E., Steinberg, S.M., Jain, L., Annunziata, C.M., Minasian, L., Sarosy, G., Kotz, H.L., Premkumar, A., Cao, L., McNally, D., Chow, C., Chen, H.X., Wright, J.J., Figg, W.D., Kohn, E.C. (2008) Combination Targeted Therapy With Sorafenib and Bevacizumab Results in Enhanced Toxicity and Antitumor Activity. J Clin Oncol. Vol. 26(22):3709-14.

vascular endothelial growth factor, ovarian cancer



Analytes tested using MSD assays: User developed VEGF assay on MSD avidin coated plates
Matrix tested: Human serum and plasma
Summary: This paper provides the results of a clinical trial to test whether Sorafenib (Raf kinase inhibitor) and Bevacizumab (anti-VEGF antibody) would act in an additive manner against the VEGF pathway so that they can be used as combination therapy in patients with solid tumors.
Collings, F.B., Vaidya, V.S. (2008) Novel technologies for the discovery and quantitation of biomarkers of toxicity. Toxicology. Vol. 245(3):167-74.

toxicoproteomics, metebolomics, software



Summary: This paper reviews the new methods available for the discovery and validation of biomarkers, which significantly reduce assay time and cost and improve the sensitivity of screening methods. ELISA, FAST Quant, SearchLight, MESO SCALE DISCOVERY®, Luminex, silicon nanowire and patterned paper based assays have been discussed here as available technologies for quantitation of markers.
Dao, J.H., Kurzeja, R.J., Morachis, J.M., Veith, H., Lewis, J., Yu, V., Tegley, C.M., Tagari, P. (2008) Kinetic characterization and identification of a novel inhibitor of hypoxia-inducible factor prolyl hydroxylase 2 using a time-resolved fluorescence resonance energy transfer-based assay technology. Anal Biochem. Vol. 384(2):213-23.

electrochemiluminescence, homogeneous time resolved fluorescence resonance energy transfer, TR-FRET



Analytes tested using MSD assays: User developed assay for Km determination of recombinant hydroxylated HIF-1alpha peptide
Matrix tested: Assay buffer
Summary: In this study, the authors developed a novel and high-throughput ECL assay as well as a homogeneous time resolved FRET assay to enzymatically characterize the full-length recombinant human hypoxia-inducible factor prolyl hydroxylases 2 (HIF–PHD2).
Dieterle, F., Marrer, E. (2008) New technologies around biomarkers and their interplay with drug development. Anal Bioanal Chem. Vol. 390(1):141-54.

MESO SCALE DISCOVERY, Luminex, VeraCode



Summary: This is a review paper that provides a critical examination of recently established platforms and technologies for biomarker development, and their applications from discovery to validation in genetics, genomics, proteomics, metabonomics and assay development.
Garber, E.A., O'Brien, T.W. (2008) Detection of ricin in food using electrochemiluminescence-based technology. J AOAC Int. Vol. 91(2):376-82.

biodefense, hook effect



Analytes tested using MSD assays: User developed assay to measure ricin on MSD Streptavidin coated plates
Matrix tested: V8 juice, orange juice, dairy products, soda, vegetables, bakery products, chocolate, condiments
Summary: In this study, the authors developed a highly sensitive and time effective assay to measure ricin in the above matrices.
Gerszten, R.E., Accurso, F., Bernard, G.R., Caprioli, R.M., Klee, E.W., Klee, G.G., Kullo, I., Laguna, T.A., Roth, F.P., Sabatine, M., Srinivas, P., Wang, T.J., Ware, L.B. (2008) Challenges in translating plasma proteomics from bench to bedside: update from the NHLBI Clinical Proteomics Programs. Am J Physiol Lung Cell Mol Physiol. Vol. 295(1):L16-22.

proteome



Summary: This paper discusses the highlights of a meeting held by the National Heart, Lung, and Blood Institute's (NHLBI) Clinical Proteomics Program committee which focused on the barriers to achieving effective translation of plasma protein biomarkers from discovery to clinical use, and the strategies for overcoming these challenges. The strengths and limitations of multiplexing platforms, including planar assays, bead-based assays and mass spectrometry, have been reviewed.
Karbanova, J., Missol-Kolka, E., Fonseca, A.V., Lorra, C., Janich, P., Hollerova, H., Jaszai, J., Ehrmann, J., Kolar, Z., Liebers, C., Arl, S., Subrtova, D., Freund, D., Mokry, J., Huttner, W.B., Corbeil, D. (2008) The Stem Cell Marker CD133 (Prominin-1) Is Expressed in Various Human Glandular Epithelia. J Hist Cytochem. Vol. 56(11):977–993.
Analytes tested using MSD assays: Monoclonal antibody to human prominin-1
Matrix tested: Hybridoma supernatants
Summary: In this study, the authors investigated the expression profile of prominin-1, which is expressed in various somatic stem cells and progenitor cells, in human glandular epithelia using a new monoclonal antibody. MSD technology was for hybridoma screening of monoclonal antibodies to prominin-1.
Newland, N., Richter, A. (2008) Agents associated with lung inflammation induce similar responses in NCI-H292 lung epithelial cells. Toxicol In Vitro. Vol. 22(7):1782-8 (British American Tobacco).

Interleukin, IL6, IL8



Analytes tested using MSD assays: IL-6, IL-8
Matrix tested: Cell culture supernatant
Summary: In this study, the authors examined the ability of a lung epithelial model to respond to lung toxicants including cigarette smoke total particulate matter, fly ash, bleomycin, lipopolysaccharide, vanadyl sulphate, diesel exhaust particles, and carbon black.
O'Brien, P.J. (2008) Cardiac troponin is the most effective translational safety biomarker for myocardial injury in cardiotoxicity. Toxicology. Vol. 245(3):206-18.

cTnI, cTnT



Summary: This review paper assessed and compared the different biomarkers for myocardial injury and cardiotoxicity, and showed that cardiac Troponin scored much higher than the rest and therefore must be selected as the gold standard biomarker. It has been noted that cardiac Troponin T assays are commercially produced by two vendors only, one being MSD and the other is Roche Diagnostics.
Rottenberg, S., Jaspers, J.E., Kersbergen, A., van der Burg, E., Nygren, A.O., Zander, S.A., Derksen, P.W., de Bruin, M., Zevenhoven, J., Lau, A., Boulter, R., Cranston, A., O'Connor, M.J., Martin, N.M., Borst, P., Jonkers, J. (2008) High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. PNAS Vol. 105(44):17079-17084.

Poly ADP ribose polymerase 1



Analytes tested using MSD assays: PARP1
Matrix tested: Tumor xenograft lysates
Summary: In this study, the effects of PARP inhibitor, AZD2281, have been tested in a genetically engineered mouse model (GEMM) for BRCA1-associated breast cancer.
Russell, C.B., Suggs, S., Robson, K.M., Kerkof, K., Kivman, L.D., Notari, K.H., Rees, W.A., Leshinsky, N., Patterson, S.D. (2008) Biomarker Sample Collection and Handling in the Clinical Setting to Support Early-Phase Drug in Biomarker Methods in Drug Discovery and Development; Humana Press: 1-26.

Summary: This review provides an insight into the various aspects of biomarker analysis that need to be considered for generating robust data for pharmacodynamic studies. The issues discussed include sample selection, sample collection, and fit-for-purpose assay qualification.
Vicini, J, Etherton, T., Kris-Etherton, P., Ballam, J., Denham, S., Staub, R., Goldstein, D., Cady, R., McGrath, M., Lucy, M. (2008) Survey of retail milk composition as affected by label claims regarding farm-management practices. J Am Diet Assoc. Vol. 108(7):1198-203.
Analytes tested using MSD assays: Insulin-like growth factor-1 (IGF-1), bovine somatotropin (bST)
Matrix tested: Milk
Summary: This study is based on a survey that was conducted to compare the quality (antibiotics and bacterial counts), nutritional value (fat, protein, and solids-not-fat), and hormonal composition (somatotropin, insulin-like growth factor-1, estradiol, and progesterone) of conventional milk, recombinant bovine somatotropin free milk, and organic milk.
Wei, J.S., Badgett, T.C., Khan, J. (2008) New technologies for diagnosing pediatric tumors. Expert Opin Med Diagn. Vol. 2(11):1205-1219.

bead based detection, genomic hybridization, isotope coded affinity tags, label free detection, DNA sequencing, MESO SCALE DISCOVERY, microarray, microRNA, polymerase chain reaction, reverse phase protein array, RT-PCR



Summary: This is a review paper that provides a discussion of new technologies including DNA microarray, multiplexed PCR, bead based assays, and protein detection methods that can be applied to the discovery of biomarkers related to the diagnosis of pediatric cancers.
Batchelor, T., Sorensen, A.G., di Tomaso, E., Zhang, W.T., Duda, D.G., Cohen, K.S., Kozak, K.R., Cahill, D.P., Chen, P.J., Zhu, M., Ancukiewicz, M., Mrugala, M.M., Plotkin, S., Drappatz, J., Louis, D.N., Ivy, P., Scadden, D.T., Benner, T., Loeffler, J.S., Wen, P.Y., Jain, R.K. (2007) AZD2171, a Pan-VEGF receptor tyrosine Kinase Inhibitor, Normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell. Vol. 11(1):83-95.

vascular endothelial growth factor receptor, placental growth factor, basic fibroblast growth factor



Analytes tested using MSD assays: VEGF, PlGF, soluble VEGFR1, bFGF
Matrix tested: Human plasma
Summary: This study used MRI techniques to report an immediate and significant normalizing effect of AZD2171 (an oral tyrosine kinase inhibitor of VEGF receptors) in 16 patients with recurrent glioblastoma, with promising tumor responses and biomarker correlations.
Burkhardt, M., Lopez-Acosta, A., Reiter, K., Lopes, V., Lees A. (2007) Purification of soluble CD14 fusion proteins and the use in an electrochemiluminescent assay for lipopolysaccharide binding. Protein Expr Purif. Vol. 51(1):96-101.

Lipopolysaccharide



Analytes tested using MSD assays: User developed assay to measure LPS binding to CD-14
Matrix tested: Assay buffer
Summary: In this study, the authors developed a method for the purification of CD14 (lipopolysaccharide binding protein), and an electrochemiluminescence based assay on the MSD platform to measure the binding of bioactive LPS to CD14. The authors highlighted the dynamic range, minimal washing steps, speed and versatility of the MSD assay.
Guglielmo-Viret, V., Thullier, P. (2007) Comparison of an electrochemiluminescence assay in plate format over a colorimetric ELISA, for the detection of ricin B chain (RCA-B). J Immunol Methods. Vol. 328(1-2):70-8.

bead based assay



Analytes tested using MSD assays: User developed assay for ricin B-chain
Matrix tested: Assay buffer
Summary: In this study, an ECL based assay was developed for the B chain of ricin (RCA-B) on the MSD platform, and this assay was compared to colorimetric ELISA. The ECL assay was shown to be 8-fold more sensitive, had less matrix effects, more robust and was faster than the corresponding ELISA.
Rosen, L., Kurzrock, R., Mulay, M., Van Vugt, A., Purdom, M., Ng, C., Silverman, J., Koutsoukos, A., Sun, Y.N., Bass, M.B., Xu, R.Y., Polverino, A., Wiezorek, J.S., Chang, D.D., Benjamin, R., Herbst, R.S. (2007) Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors. J Clin Oncol. Vol. 25(17):2369-76.

vascular endothelial growth factor receptor, placental growth factor, basic fibroblast growth factor, sKit



Analytes tested using MSD assays: VEGF, PlGF, soluble VEGFR1, bFGF, soluble VEGFR2, soluble Kit
Matrix tested: Human serum
Summary: This study is based on a phase I, open-label, sequential dose-escalating clinical trial of AMG 706 (inhibits VEGFR1, VEGFR2, VEGFR3, PlGF receptor, and Kit) in patients with advanced solid tumors, and demonstrated the tolerability, anti-tumor activity and favorable pharmacokinetics of AMG 706.
Shi, M. (2007) Biomarker Development Strategies - surmounting scientific and regulatory barriers in bringing innovative medicine to market. IDrugs. Vol. 10(4):246-8.
Summary: This paper provides the highlights of Biomarker Development Strategies conference held in Washington DC on 29th and 30th of December 2007, which focused on the progress of biomarker strategies and regulatory frameworks that enable decision-making in pharmaceutical development and early diagnosis of disease. MSD platform was highlighted for its use in the phase I clinical trial of AMG-706, wherein, plasma vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFG)F, placental growth factor (PlGF), c-Kit, sFlt-1 and soluble kinase insert domain receptor (sKDR) were measured by using multiplex assays.
Wu, S.J., Schmidt, A., Beil, E.J., Day, N.D., Branigan, P.J., Liu, C., Gutshall, L.L., Palomo, C., Furze, J., Taylor, G., Melero, J.A., Tsui, P., Del Vecchio, A.M., Kruszynski, M. (2007) Characterization of the epitope for anti-human respiratory syncytial virus F protein monoclonal antibody 101F using synthetic peptides and genetic approaches. J Gen Virol. Vol. 88(Pt 10):2719-23.

anti-human respiratory syncytial virus, palivizumab, chimeric 101F



Analytes tested using MSD assays: User developed assay to detect binding of RSV F-protein peptides to anti-RSV drug
Matrix tested: Assay buffer
Summary: In this study, the epitope on the human RSV F-glycoprotein recognized by a neutralizing monoclonal antibody, ch101F, was mapped by using three methods: a) binding of the synthetic peptides covering the amino acid 422–438 sequence region of F protein; b) binding to recombinant F proteins expressed at the cell surface and containing mutations at positions 427, 429 and 433; and c) selection of antibody escape mutant viruses.
Wang, X., Simmons, H. A., Salatto, C. T., Cosgrove, P. G., Thompson, D. D. (2006) Lasofoxifene enhances vaginal mucus formation without causing hypertrophy and increases estrogen receptor [beta] and androgen receptor in rats. Menopause. Vol. 13(4):609-620.

Lasofoxifene



Analytes tested using MSD assays: Estrogen receptor (ER), Estrogen receptor beta (ERß), progesterone receptor (PR), androgen receptor (AR)
Matrix tested: Rat vaginal homogenates
Summary: The focus of this study was to elucidate the molecular and cellular basis of the unique effects of Lasofoxifene, a selective estrogen-receptor modulator (SERM), in OVX immature rat model. Lasofoxifene showed efficacy in vaginal and vulvar atrophy.
Wilkinson-Berka, J. L., Jones, D., Taylor, G., Jaworski, K., Kelly, D. J., Ludbrook, S. B., Willette, R. N., Kumar, S., Gilbert, R.E. (2006) SB-267268, a Nonpeptidic Antagonist of vß3 and vß5 Integrins, Reduces Angiogenesis and VEGF Expression in a Mouse Model of Retinopathy of Prematurity. Invest Ophthalmol Vis Sci. Vol. 47(4):1600-5.

angiogenesis



Analytes tested using MSD assays: Integrin / ligand binding assay
Matrix tested: Assay buffer
Summary: This study examined whether the administration of SB-267268 (antagonist of avß3 and avß5 integrins) reduces retinal angiogenesis in mice with ROP and alters the expression of retinal VEGF and VEGFR2.
Willett, C.G., Boucher, Y., Duda, D.G., di Tomaso, E., Munn, L.L., Tong, R.T., Kozin, S.V., Petit, L., Jain, R.K., Chung, D.C., Sahani, D.V., Kalva, S.P., Cohen, K.S., Scadden, D.T., Fischman, A.J., Clark, J.W., Ryan, D.P., Zhu, A.X., Blaszkowsky, L.S., Shellito, P.C., Mino-Kenudson, M., Lauwers, G.Y. (2005) Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J Clin Oncology. Vol. 23(31): 8136-8139.

vascular endothelial growth factor receptor, placental growth factor



Analytes tested using MSD assays: VEGF, PlGF
Matrix tested: Human plasma
Summary: This study provides the results of a clinical trial where patients with advanced rectal carcinoma were treated with Bevacizumab at 10 mg/kg on day 1, given concurrent administration of Bevacizumab on days 15, 29, 43 along with fluorouracil chemotherapy and pelvic radiation therapy.

* Pub Med (www.pubmed.gov) is a service of the U.S. National Library of Medicine and the National Institutes of Health



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