Medical

Theranostic profiling for actionable aberrations in advanced high risk osteosarcoma with aggressive biology reveals high molecular diversity: the human fingerprint hypothesis ABSTRACT The survival of patients with advanced osteosarcoma is poor with limited therapeutic options. There is an urgent need for new targeted therapies based on biomarkers. Recently, theranostic molecular profiling services for cancer patients by CLIA-certified commercial companies as well as in-house profiling in academic medical centers have expanded exponentially. We evaluated molecular profiles of patients with advanced osteosarcoma whose tumor tissue had been analyzed by one of the following methods: 1. 182-gene next-generation exome sequencing (Foundation Medicine, Boston, MA), 2. Immunohistochemistry (IHC)/PCR-based panel (CARIS Target Now, Irving, Tx), 3.Comparative genome hybridization (Oncopath, San Antonio, TX). 4. Single-gene PCR assays,  PTEN  IHC (MDACC CLIA), 5. UT Houston morphoproteomics (Housto

Oncoscience   journal MISSION Oncoscience's mission is to cover the rapidly growing field of cancer research. We aim to focus on emergent topics not currently covered by other journals. Oncoscience has also a special mission: freeing researchers in oncology from publication costs. It is free for both readers and authors. Launched in 2014, Oncoscience is a peer-reviewed, traditional-style, bi-monthly journal with free access. Oncoscience also has a special mission: freeing researchers in oncology from publication costs. It is free for both readers and authors. As a traditional journal, Oncoscience publishes papers online in issues with page numbers. Each issue/paper can be printed upon special request. All Oncoscience content is archived in  PubMed Central . The publisher also maintains the  journal's own digital archive . Oncoscience is indexed/abstracted in PubMed, PubMed Central, Scopus (Oncology category), and EMBASE. In 2018, Oncoscience was invited to participate and is no

Enhancement of Folate Receptor α Expression in Tumor Cells Through the Glucocorticoid Receptor: A Promising Means to Improved Tumor Detection and Targeting Abstract The utility of the folate receptor (FR) type α, in a broad range of targeted therapies and as a diagnostic serum marker in cancer, is confounded by its variable tumor expression levels. FR-α, its mRNA and its promoter activity were coordinately up-regulated by the glucocorticoid receptor (GR) agonist, dexamethasone. Optimal promoter activation which occurred at <50 nmol/L dexamethasone was inhibited by the GR antagonist, RU486, and was enhanced by coactivators, supporting GR mediation of the dexamethasone effect. The dexamethasone response of the FR-α promoter progressed even after dexamethasone was withdrawn, but this delayed effect required prior  de novo  protein synthesis indicating an indirect regulation. The dexamethasone effect was mediated by the G/C-rich (Sp1 binding) element in the core P4 promoter and was opti

The Human Multidrug Resistance Protein MRP5 Transports Folates and Can Mediate Cellular Resistance against Antifolates Abstract Members of the multidrug resistance protein family, notably MRP1-4/ABCC1-4, and the breast cancer resistance protein BCRP/ABCG2 have been recognized as cellular exporters for the folate antagonist methotrexate (MTX). Here we show that MRP5/ABCC5 is also an antifolate and folate exporter based on the following evidence: (a) Using membrane vesicles from HEK293 cells, we show that MRP5 transports both MTX ( K M  = 1.3 mmol/L and  V MAX  = 780 pmol per mg protein per minute) and folic acid ( K M  = 1.0 mmol/L and  V MAX  = 875 pmol per mg protein per minute). MRP5 also transports MTX-glu 2  ( K M  = 0.7 mmol/L and  V MAX  = 450 pmol per mg protein per minute) but not MTX-glu 3 . (b) Both accumulation of total [ 3 H]MTX and of MTX polyglutamates were significantly reduced in MRP5 overexpressing cells. (c) Cell growth inhibition studies with MRP5 transfected HEK293

1′-Acetoxychavicol Acetate Is a Novel Nuclear Factor κB Inhibitor with Significant Activity against Multiple Myeloma Abstract 1′-Acetoxychavicol acetate (ACA) is a component of a traditional Asian condiment obtained from the rhizomes of the commonly used ethno-medicinal plant  Languas galanga . Here, we show for the first time that ACA dramatically inhibits the cellular growth of human myeloma cells via the inhibition of nuclear factor κB (NF-κB) activity. In myeloma cells, cultivation with ACA induced G 0 -G 1  phase cell cycle arrest, followed by apoptosis. Treatment with ACA induced caspase 3, 9, and 8 activities, suggesting that ACA-induced apoptosis in myeloma cells mediates both mitochondrial- and Fas-dependent pathways. Furthermore, we showed that ACA significantly inhibits the serine phosphorylation and degradation of IκBα. ACA rapidly decreased the nuclear expression of NF-κB, but increased the accumulation of cytosol NF-κB in RPMI8226 cells, indicating that ACA inhibits the t

A Monoclonal Antibody that Binds Anionic Phospholipids on Tumor Blood Vessels Enhances the Antitumor Effect of Docetaxel on Human Breast Tumors in Mice Abstract Anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of viable vascular endothelial cells in tumors, providing an excellent marker for tumor vascular targeting. We recently raised an IgG monoclonal antibody, 3G4, which binds to anionic phospholipids in a β2-glycoprotein I–dependent manner. It inhibited tumor growth in a variety of rodent tumor models by stimulating antibody-dependent cellular cytotoxicity toward tumor vessels. In the present study, we tested the hypothesis that docetaxel, which is known to have antivascular effects on tumors, might induce exposure of anionic phospholipids on tumor vasculature and, thus, enhance the antitumor activity of 3G4. Treatment of human umbilical vascular endothelial cells with subtoxic concentrations of docetaxel (20 pmol/L)  in vitro  caused ani