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Newark, DE, United States

Seyhan A.A.,Pfizer | Varadarajan U.,Pfizer | Choe S.,Agios Pharmaceuticals | Liu Y.,Pfizer | And 8 more authors.
Molecular BioSystems | Year: 2011

ErbB2 is frequently activated in tumors, and influences a wide array of cellular functions, including proliferation, apoptosis, cell motility and adhesion. HKI-272 (neratinib) is a small molecule pan-kinase inhibitor of the ErbB family of receptor tyrosine kinases, and shows strong antiproliferative activity in ErbB2-overexpressing breast cancer cells. We undertook a genome-wide pooled lentiviral RNAi screen to identify synthetic lethal or enhancer (synthetic modulator screen) genes that interact with neratinib in a human breast cancer cell line (SKBR-3). These genes upon knockdown would modulate cell viability in the presence of subeffective concentrations of neratinib. We discovered a diverse set of genes whose depletion selectively impaired or enhanced the viability of SKBR-3 cells in the presence of neratinib. We observed diverse pathways including EGFR, hypoxia, cAMP, and protein ubiquitination that, when co-treated with RNAi and neratinib, resulted in arrest of cell proliferation. Examining the changes of these genes and their protein products also led to a rationale for clinically relevant drug combination treatments. Treatment of cells with either paclitaxel or cytarabine in combination with neratinib resulted in a strong antiproliferative effect. The identification of novel mediators of cellular response to neratinib and the development of potential drug combination treatments have expanded our understanding of neratinib's mode-of-action for the development of more effective therapeutic regimens. Notably, our findings support a paclitaxel and neratinib phase III clinical trial in breast cancer patients. © 2011 The Royal Society of Chemistry.


Parker G.C.,Wayne State University | Parker G.C.,iBio Inc | Carruthers N.J.,Wayne State University | Gratsch T.,Wayne State University | And 2 more authors.
Journal of Neural Transmission | Year: 2016

Spinal muscular atrophy is an autosomal recessive motor neuron disease caused by a genetic defect carried by as many as one in 75 people. Unlike most neurological disorders, we know exactly what the genetic basis is of the disorder, but in spite of this, have little understanding of why the low levels of one protein, survival motor neuron protein, results in the specific progressive die back of only one cell type in the body, the motor neuron. Given the fact that all cells in the body of a patient with spinal muscular atrophy share the same low abundance of the protein throughout development, an appropriate approach is to ask how lower levels of survival motor neuron protein affects the proteome of embryonic stem cells prior to development. Convergent biostatistical analyses of a discovery proteomic analysis of these cells provide results that are consistent with the pathomechanistic fate of the developed motor neuron. © 2016 Springer-Verlag Wien


Patent
iBio Inc | Date: 2015-01-22

The present invention provides trans-complementation systems for expressing gene products in plants. In general, the invention provides systems including a carrier vector and a producer vector, both based on plant viruses. The producer vector is defective for at least one function needed for successful systemic infection of a plant, e.g., replication, cell-to-cell movement, or long distance movement. The carrier vector supplies the missing function in trans. Certain producer vectors lack a functional coat protein coding sequence, in which case the corresponding producer vector supplies coat protein in trans. The invention also provides novel plant viral vectors and methods of use, e.g., to produce polypeptides or active RNAs in plants.


Patent
iBio Inc | Date: 2013-12-02

The present invention provides trans-complementation systems for expressing gene products in plants. In general, the invention provides systems including a carrier vector and a producer vector, both based on plant viruses. The producer vector is defective for at least one function needed for successful systemic infection of a plant, e.g., replication, cell-to-cell movement, or long distance movement. The carrier vector supplies the missing function in trans. Certain producer vectors lack a functional coat protein coding sequence, in which case the corresponding producer vector supplies coat protein in trans. The invention also provides novel plant viral vectors and methods of use, e.g., to produce polypeptides or active RNAs in plants.


Antibodies against influenza neuraminidase, compositions containing the antibodies, and methods of using the antibodies are provided herein.

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