Posters
K. Bernards, Y. Ovechkina, J. Cheng, J. Kushleika, A. Angione, J. Hnilo, C. O’Day, U. Warrior, J. Baumgartner
Activated kinases that induce cell proliferation have been attractive targets for targeted cancer therapy development. Cancer cells could become dependent on tumor-specific activated kinases and this tendency has been described as oncogene addiction. Here, we investigated four activated kinase inhibitors: BRAF inhibitor, PLX403 analog, Sorafenib and the MEK inhibitors, CI1040 and PD0325901.
Yulia Y. Ovechkina, Christine O’Day, Karen Marcoe, Robert Keyser, Karen Bernards, Jessica Chesnut-Speelman, Phuong T.B. Nguyen, Jenny Mulligan, Teddy Lin, Rodney Shively, Jim Hnilo, Brian Nelson
In vitro cellular response profiling of tumor human cell lines has become a widely used approach for the targeted cancer therapeutics development. Correlation of the drug sensitivity and resistance cellular response with genomic data offers a robust and sensitive system for predicting clinical efficacy and identifying more efficacious patient populations.
C. Thuilliez, M. Perron-Lepage, C. Clément, C. Botteron
The standard procedure for microscopic evaluation of intramuscular injection sites at our Laboratory involves the examination of three tissue pieces from each site, in order to maximise the chance of examining the area where the injected material was deposited.
Ovechkina Y., Keyser R., Marcoe K., Nguyen P., Chesnut-Speelman J., Bernards K., Yoshino K., Nelson B.,
Lin T., Hnilo J., Shively R., Mulligan J., Harges, M., and Christine O’Day
In vitro cellular response profiling of tumor human cell lines has become a widely used approach for the targeted cancer therapeutics development. Correlation of the drug sensitivity and resistance cellular response with genomic data offers a robust and sensitive system for predicting clinical efficacy and identifying more efficacious patient populations.
High Throughput Cell Line Profiling for Identification of Anticancer Drug Sensitivity and Resistance Biomarkers: OncoPredictor ™
U. Warrior, Y. Ovechkina, K. Marcoe, R. Keyser, K. Yoshino, P. Nguyen, J. Hnilo, R. Shively, J. Mulligan, K. Bernards, T. Lin, S. Wang, J. Chesnut-Speelman, S. Sadis, D. Rhodes, and C. O’Day
Tumor derived cell lines have been in use for cancer drug profiling as evidenced by the establishment of NCI-60 panel as a drug discovery tool in early 1990s. In recent years, due to the advancement of targeted therapies in cancer, screening of larger cell panels with greater genetic heterogeneity has become very important not only to measure efficacy of the compounds, but also for identifying the biomarkers that are responsible for the efficacy.
Profiles of Contributing Genes to Sensitive/Resistant Phenotype of 11 Different Oncology Therapeutic Agents Across 240 Cell Lines
C. O’Day, Y. Ovechkina, K. Marcoe, R. Keyser, K. Yoshino, P. Nguyen, J. Hnilo, R. Shively, J. Mulligan, K. Bernards, J. Chesnut-Speelman, T. Lin, and S. Wang
A number of targeted therapies have been shown to be effective in the treatment of cancer, such as Imatinib for treating chronic myelogenous leukemia, Erlotinib for non-small-cell lung cancers and Sorefinib for metastatic lung cancer.
Elucidation of Cytokine Storm: The Effect of In-Vitro Antibody Immobilization Methods on
Cytokine Secretion in a Cell-Based Assay
J. Mulligan, R. Shively, and C. O’Day
Cytokine storm is a severe, potentially life-threatening immune reaction resulting from an abnormal cascade of pro-inflammatory cytokine release. In a typical inflammatory event, cytokines released in response to a biological threat are kept in check by a feedback loop.
Assessing Cancer Therapeutic Agents Across a Fifteen Human Tumor Cell Line Panel
Y. Ovechkina, P. Nguyen, F. Keyser, R. Shively, K. Marcoe, and C. O’Day
The integration of mutation profiling data (Sanger Institute) with the cellular response phenotypes generated with this multiparametric OncoPanel profiling assay allowed investigation of mechanisms of enhanced susceptibility to anticancer agents.
Characterization of Kinase Inhibitors by In Vitro and Functional Cellular Assays[link to (open in new window)]
G. Castillo, J. Hnilo, S. Bounds, M. Gross, K. Yoshino and L. Martel
Abnormal protein phosphorylation has been implicated in the etiology or progression of a broad spectrum of major disorders and diseases. The drug discovery industry has embraced kinase screening with the goal of finding inhibitors of clinically relevant kinases.
Drug Profiling Across Multiple Tumor Cell Lines from Six Different Tissue Origins to Investigate Sensitivity and Cellular Mechanism of Action
C. O’Day, Y. Ovechkina, P. Nguyen, R. Keyser, R. Shively, R. Rodriguez, J. Alfonso, K. Yoshino, K. Marcoe, C. Ward and D. Kirk
The NCI has developed a model of 60 cell lines to test the proliferation index of cancer cells in response to anticancer agents. Proliferation, though important, can only tell part of the story, as the mechanism for this apparent lack of growth is missing.
Discovery P450 Inhibition Screening: How Does A 5-in-1 LC-MS/MS Assay Compare to Commonly Used Fluorometric Assays?
K. Rogers, J. Woodson and D. Mautz
In this study, we compare five commonly used fluorometric assays that use expression system microsomes to an LC-MS-based method that utilizes pooled human liver microsomes and a 5-in-1 substrate cassette. The apparent advantages of the latter method are its similarity to single substrate methods used in preclinical evaluation and the uniformity of the assay conditions.
Endogenous Receptor Characterization in Normal Lung Cells by Cellular Dielectric Spectroscopy and RNA Interference
S. Bounds, M. Gross
Functional cellular assays facilitate early assessment of lead compound potency and selectivity, a critical process in drug development. Cellular dielectric spectroscopy (CDS) provides sensitive measurement of downstream functional responses to cell surface receptor activation in living cells as they respond to unlabeled ligands in real time.
An Efficient Scalable Process for the Synthesis of (+)-trans-4-1(1-Benzyloxycarbonylaminoethyl)-cyclohexanecarboxylic Acid
D. Gopal, K. Maslanka, S. Krumins, H. Wu, B.Wicks, J. McRea, W. Weiner
The process development of a route for preparing(+)-trans-4-1(1-benzyloxycarbonylaminoethyl)-cyclohexanecarboxylic acid in kilogram quantities is described 25% overall yield using ®-(+)-1-phenyl-ethylamine as the starting material.
Evaluation of Cardiac Liability of Drugs by Two In Vitro Functional Assays
S. Wang, T. Lin, K. Bernards, Y.Ovechkina, C. O’Day and D. Small
Drug induced cardiotoxic effects including delayed cardiac repolarization may induce arrhythmias such as Torsades de Pointes or even sudden death. It is a challenge to detect these side effects of compounds at the early stage of drug development in the pharmaceutical industry.
Multiparametric Hepatotoxicity Screening in HepG2 Cells with Comparison in Primary Hepatocytes
K. Marcoe, Y. Ovechkina, R. Keyser, P. Nguyen, C. O’Day
Recognition of drug-induced hepatotoxic potential early in the drug development cascade creates opportunities for ranking and prioritizing, or developing alternatives with lower toxicity. Detection of hepatic apoptosis induction, phospholipidosis and neutral lipid accumulation late in the drug development pipeline has contributed to late-stage drug failures.
In Vitro Evaluation of the Anti-EGFR Antibody Cetuximab and the Anti-HER2 Antibody
Trastuzumab in a Panel of Human Tumor Cell Lines
K. Marcoe, Y. Ovechkina, R. Keyser, K. Bernards, J. Chesnut-Speelman, K. Yoshino, and C. O’Day
Greater understanding of specific cellular, molecular and genetic mechanisms that regulate cancer growth and progression has allowed design of molecular targeting strategies for cancer therapy with increased tumor specificity. Epidermal growth factor receptor (EGFR) signaling inhibition has been one of the most extensively investigated molecular oncology targets.
In Vitro Multiparameter Hepatotoxicity Assay Development In Human Primary Hepatocytes And Hepg2 Cells With S9 Liver Fractions
K. Marcoe, H. Garside, J. Chesnut-Speelman, A. Foster, Y. Ovechkina, U. Warrior, J. Kenna, J. Bowes, and C. O’Day
In this study, multiplexed high content screening (HCS) with automated fluorescence microscopy and image analysis based technology was used to develop and evaluate cellular assays that detect key mechanisms considered relevant to DILI.