Schayowitz A.,University of Maryland, Baltimore |
Schayowitz A.,Biomarker Strategies |
Sabnis G.,University of Maryland, Baltimore |
Goloubeva O.,University of Maryland, Baltimore |
And 3 more authors.
British Journal of Cancer | Year: 2010
Background:To determine the mechanisms associated with loss of androgen dependency and disease progression in prostate cancer (PCa), we investigated the relationship between the androgen receptor (AR) and mTOR pathways and the impact of inhibiting both pathways in androgen-dependent and castration-resistant PCa models.Experimental design:Androgen-dependent (LNCaP) and castration-resistant PCa (HP-LNCaP) cells were grown as tumours in SCID mice. Once tumours reached 500 mm 3, animals were grouped and injected subcutaneous with vehicle, our novel anti-androgen/androgen synthesis inhibitor, VN/124-1, bicalutamide, and everolimus. Tumour volumes were measured biweekly. The PSA and protein analyses were performed after completion of the treatment.Results:The addition of everolimus to bicalutamide treatment of resistant tumours significantly reduced tumour growth rates and tumour volumes. Anti-androgen treatment also increased protein expression of multiple signal transduction pathways earlier than vehicle-treated control xenografts. VN/124-1 plus everolimus acted in concert to reduce tumour growth rates in our castration-resistant xenograft model.Conclusions:This study suggests that dual inhibition of AR and mTOR in castration-resistant xenograft models can restore sensitivity of tumours to anti-androgen therapy. Furthermore, after bicalutamide failure, dual inhibition with VN/124-1 and everolimus was the most effective treatment. © 2010 Cancer Research UK. All rights reserved.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 192.79K | Year: 2011
Most of the currently utilized predictive biomarkers for therapeutic decision-making provide information about the presence or absence of the drug target, but reveal little about the functional circuitry of the signaling network that the drug must also impact. Ex vivo biomarkers are dynamic molecular markers evoked from living tumor cells after removal from the patient. Such ex vivo biomarkers provide valuable mechanistic information that may facilitate drug development and guide the clinical selection of targeted therapeutics. We propose to develop a companion diagnostic test, named SnapMap, for drugs targeting the ErbB signal transduction network. This test will utilize tumor biopsy samples processed on the SnapPath tumor processing system to evoke ex vivo biomarkers from live tumor samples.
Biomarker Strategies | Date: 2012-11-20
Chemical reagents not for medical use, namely, peptide and nucleic acid based probes for use in laboratory analysis of biological fluids, cells and tissues. Clinical laboratory instruments for analysis of biological fluids, cells and tissues; laboratory plates, glass slides, tubes and chips for use in multi-well arrays for use in analysis of blood and other fluids. Medical device for collection and storage of biological fluids, cells or tissues for laboratory analysis. Scientific research for the development of new pharmaceutical products; custom design and development of chemical reagents and assay platforms for use in analysis of biological fluids, cells and tissues.
Biomarker Strategies | Date: 2007-06-29
Assays and reagents for use in genetic research; Biochemical reagents commonly known as probes, for detecting and analyzing molecules in protein or nucleotide arrays; Reagents for research purposes; Reagents for scientific or medical research use; Reagents for use in scientific apparatus for chemical or biological analysis. Clinical laboratory analyzers for measuring, testing and analyzing blood and other bodily fluids; Plates, glass slides or chips having multi-well arrays that can be used in chemical analysis, biological analysis or patterning for scientific, laboratory or medical research use; Apparatus for testing gas, liquids and solids. Scientific research; Scientific research and development; Scientific research in the field of genetics and genetic engineering; Chemical, biochemical, biological and bacteriological research and analysis; Custom design and development of chemical reagents and biochemical assays.
Biomarker Strategies | Date: 2015-08-20
Embodiments of the present invention are directed to improved methods and devices for analyzing a cell, aggregated cells, or a solid tumor. Such methods and devices are, for example, useful in the field of pathology and can provide improved cell processing and analytical results.