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

FOUNDING ONCOTARGET EDITORIAL BOARD MEMBERS WIN 2019 NOBEL PRIZE October 11, 2019   Oncotarget NEW YORK, October 11, 2019 – The 2019 Nobel Prize in Physiology or Medicine has been awarded jointly to  Oncotarget  Editorial Board Members  William G. Kaelin Jr., and Gregg L. Semenza  for their discoveries of “how cells sense and adapt to oxygen availability.” The pair was named alongside UK physician-scientist Sir Peter J. Ratcliffe.  The Nobel Committee made the announcement Monday at the Karolinska Institute in Stockholm  and the discoveries have implications for how we understand and potentially treat a range of conditions like cancer, heart attack, stroke and anemia. The Nobel Laureates identified molecular machinery that regulates the activity of genes in response to varying levels of oxygen. Both William G. Kaelin and Gregg L. Semenza are founding members of Oncotarget, launched in 2010.  Oncotarget  is a weekly peer-reviewed open access bio-medical journal covering research on all

Misha Blagosklonny Senior Scientist at  Ordway Research Institute Ordway Research Institute Biotechnology https://www.apollo.io/people/Misha/Blagosklonny/57de39efa6da987b015ccadb When general population speak of modern medicine, accuracy plays one of the most crucial roles and human lives are literally dependent on it. Hence, any researches related to medicine are required to meet the top standards. The issue today is that any outcomes of researches can be shared online and used as a reference without being precisely checked and approved. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this problem and attempted to come up with an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been established back in 2010. The major principle of this journal is related to Altmetric scores that are used as a quality indicator. That allows both readers and authors to quality-check publications with Altmetric Article Reports that generat

Distinguished physician-scientist, Dr. Mikhail  Blagosklonny , joins Roswell Park Cancer Institute Mikhail (Misha) V.   Blagosklonny , MD, PhD, has been appointed Member/Professor of Oncology at Roswell Park Cancer Institute, Buffalo, NY. His appointment started April 15, 2009. Dr.  Blagosklonny  is an author of over 170 research articles, reviews and book chapters. He is Founding Editor and Editor-in-Chief of Cell Cycle and also Associate Editor of Cancer Biology & Therapy, Cancer Research, Cell Death & Differentiation, Autophagy, International Journal of Cancer, American Journal of Pathology, and PLOS ONE. His research interests range from  Cellular senescence happens in 2 steps: cell cycle arrest followed, or sometimes preceded, by gerogenic conversion (geroconversion). Geroconvesrion is a form of growth, a futile growth during cell cycle arrest. It converts reversible arrest to irreversible senescence. Geroconversion is driven by growth-promoting, mitogen-/nutrient-sensing

Author Profile Mikhail Blagosklonny Mikhail V. Blagosklonny, M.D., PhD, Professor of Oncology at Roswell Park Cancer Institute, Buffalo, NY, USA, is an author of more than 250 scientific papers on cancer and aging, with h-index 93 (google scholar). Currently, he serves as Editor-in-Chief of Cell Cycle, Oncotarget and Aging. https://blogs.biomedcentral.com/blog/author/mikhailblagosklonny/ When public speak of modern medicine, precision plays one of the most important roles and human lives are directly dependent on it. Hereby, any researches related to medicine are necessary to comply with the top standards. The problem today is that any results of researches can be posted online and used as a reference without being properly checked and approved. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this challenge and tried to develop an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been established back in 2010. The key pr