title: Analysis of two pharmacodynamic biomarkers using acoustic micro magnetic particles on the ViBE bioanalyzer.
abstract: Pharmacodynamic responses to drug treatment are often used to confirm drug-on-target biological responses. Methods ranging from mass spectrometry to immunohistochemistry exist for such analyses. By far, the most extensively used methodologies employ antigen-specific antibodies for detection (at a minimum) and, in some cases, target quantitation as well. Using a novel frequency-modulating technology from BioScale called acoustic micro magnetic particle (AMMP) detection, two pathway biomarkers were chosen for pharmacodynamic analysis and compared with either AlphaScreen or LI-COR Western blot assays. For these studies, pharmacodynamic biomarkers for both proteasome and phosphoinositol 3-kinase inhibition were used. Our results show clearly that the BioScale technology is a robust and rapid method for measuring recombinant standards or endogenously derived proteins from both tissue culture and mouse xenograft tumor lysates. Moreover, the sensitivity obtained with the BioScale platform compares favorably with LI-COR Western blot and AlphaScreen technologies. Furthermore, the use of the ViBE Bioanalyzer eliminates the labor-intensive effort of Western blot analysis and is devoid of the optical and other endogenous interfering substances derived from lysates of xenograft tumors typically observed with AlphaScreen.
authors.affiliation: Millennium Pharmaceuticals: The Takeda Oncology Company, Cambridge, MA 02139, USA.
authors.forename: Zhong-Hua
authors.initials: ZH
authors.lastname: Yan
authors.forename: Lara L
authors.initials: LL
authors.lastname: Madison
authors.forename: Anne
authors.initials: A
authors.lastname: Burkhardt
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.forename: Olga
authors.initials: O
authors.lastname: Tayber
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Dongyun
authors.initials: D
authors.lastname: Wu
authors.forename: Huay-Keng
authors.initials: HK
authors.lastname: Loke
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Wysong
authors.forename: Natalia
authors.initials: N
authors.lastname: Iartchouk
authors.forename: Michael D
authors.initials: MD
authors.lastname: Smith
authors.forename: Mike
authors.initials: M
authors.lastname: Kuranda
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Michael E
authors.initials: ME
authors.lastname: Bembenek
mesh_terms: D000162:Acoustics; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015374:Biosensing Techniques / Q000295:instrumentation*; D045744:Cell Line, Tumor; D006801:Humans; D008280:Magnetics; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054645:Protein Phosphatase 1 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D015415:Biomarkers; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C087519:PPP1R15A protein, human; D054645:Protein Phosphatase 1