archive-org.com » ORG » S » SCIENCEMAG.ORG

Total: 698

Choose link from "Titles, links and description words view":

Or switch to "Titles and links view".
  • RANKL blockade prevents and treats aggressive osteosarcomas | Science Translational Medicine
    on PubMed Search for this author on this site Sam D Molyneux Princess Margaret Cancer Centre Ontario Cancer Institute University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Trevor D McKee Spatio Temporal Targeting and Amplification of Radiation Response STTARR Program University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Paul Waterhouse Princess Margaret Cancer Centre Ontario Cancer Institute University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Josef M Penninger Institute of Molecular Biotechnology of the Austrian Academy of Sciences IMBA Dr Bohr Gasse 3 1030 Vienna Austria Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rama Khokha Princess Margaret Cancer Centre Ontario Cancer Institute University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Article Figures Data Info Metrics eLetters PDF You are currently viewing the View Full Text Username Enter your Sciencemag org username Password Enter the password that accompanies your username Forgot your username or password Log in Join Subscribe Purchase Article Activate Member Account Renew Subscription Recommend a subscription to your library Help for librarians This article has a correction Please see Erratum for the Research Article RANKL blockade prevents and treats aggressive osteosarcomas by Y Chen M A Di Grappa S D Molyneux T D McKee P Waterhouse J M Penninger R Khokha February 03 2016 Science Translational Medicine Vol 7 Issue 317 09 December 2015 Table of Contents Article Tools Email Thank you for your interest in spreading the word about Science Translational Medicine NOTE We only request your email address so that the person you are recommending the page to knows that you wanted them to see it and that it is not junk mail We do not capture any email address Your Email Your Name Send To Enter multiple addresses on separate lines or separate them with commas You are going to email the following RANKL blockade prevents and treats aggressive osteosarcomas Message Subject Your Name has forwarded a page to you from Science Translational Medicine Message Body Your Name thought you would like to see this page from the Science Translational Medicine web site Your Personal Message Send Message Download Powerpoint Print Save to my folders User Name Password Remember my user name password Submit Alerts Please log in to add an alert for this article Username Enter your Sciencemag org username Password Enter the password that accompanies your username Log in Request Permissions Citation tools RANKL blockade prevents and treats aggressive osteosarcomas By Yan Chen Marco A Di Grappa Sam

    Original URL path: http://stm.sciencemag.org/content/7/317/317ra197.figures-only (2016-02-10)
    Open archived version from archive


  • RANKL blockade prevents and treats aggressive osteosarcomas | Science Translational Medicine
    D McKee Spatio Temporal Targeting and Amplification of Radiation Response STTARR Program University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Paul Waterhouse Princess Margaret Cancer Centre Ontario Cancer Institute University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Josef M Penninger Institute of Molecular Biotechnology of the Austrian Academy of Sciences IMBA Dr Bohr Gasse 3 1030 Vienna Austria Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rama Khokha Princess Margaret Cancer Centre Ontario Cancer Institute University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Article Figures Data Info Metrics eLetters PDF Article Information vol 7 no 317 317ra197 DOI http dx doi org 10 1126 scitranslmed aad0295 PubMed 26659571 Published By American Association for the Advancement of Science Print ISSN 1946 6234 Online ISSN 1946 6242 History Received for publication 15 July 2015 Accepted for publication 23 October 2015 Copyright Usage Copyright 2015 American Association for the Advancement of Science Author Information Yan Chen 1 Marco A Di Grappa 1 Sam D Molyneux 1 Trevor D McKee 2 Paul Waterhouse 1 Josef M Penninger 3 and Rama Khokha 1 1 Princess Margaret Cancer Centre Ontario Cancer Institute University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada 2 Spatio Temporal Targeting and Amplification of Radiation Response STTARR Program University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada 3 Institute of Molecular Biotechnology of the Austrian Academy of Sciences IMBA Dr Bohr Gasse 3 1030 Vienna Austria Corresponding author E mail rkhokha at uhnresearch ca AltMetrics No Altmetric data available for this article Article usage Abstract Full PDF Dec 2015 1337 252 464 Jan 2016 564 69 157 Feb 2016 208 11 27 View Full Text Science Translational Medicine Vol 7 Issue 317 09 December 2015 Table of Contents Article Tools Email Thank you for your interest in spreading the word about Science Translational Medicine NOTE We only request your email address so that the person you are recommending the page to knows that you wanted them to see it and that it is not junk mail We do not capture any email address Your Email Your Name Send To Enter multiple addresses on separate lines or separate them with commas You are going to email the following RANKL blockade prevents and treats aggressive osteosarcomas Message Subject Your Name has forwarded a page to you from Science Translational Medicine Message Body Your Name thought you would like to see this page from the Science Translational Medicine web site Your Personal Message Send Message Download Powerpoint Print Save to my folders User Name Password Remember my user

    Original URL path: http://stm.sciencemag.org/content/7/317/317ra197.article-info (2016-02-10)
    Open archived version from archive

  • RANKL blockade prevents and treats aggressive osteosarcomas | Science Translational Medicine
    preclinical evaluation of a potential new treatment Several of the experiments and conclusions based on them caught our attention and raised questions that were not addressed either in the main text nor supplemental information Firstly the authors claim to demonstrate that osteoclast specific deletion of Rank impacted on OS The authors have used Mx1 Cre to undertake these studies and treated the mice with pIpC to induce Cre activity to delete a conditional Rank allele Whilst this is a good model for somatic deletion of Rank it is not able to be interpreted as osteoclast specific nor hematopoietic restricted There are a large number of studies demonstrating that Mx1 Cre induces recombination of loxP flanked alleles very broadly in hematopoietic cells including hematopoietic stem and progenitors skeletal stem and progenitor cells that give rise to osteoblasts and would be potentially forming the OS in these models and many other tissues in the mouse See amongst a large number of studies PMID 7660125 17574022 16754850 22385654 19322176 16598206 21123947 and https www jax org strain 005673 Furthermore the induction regimen used is considerably different from that contained in previous Show More We read with interest the recent study from Chen and colleagues describing the impact of RANKL blockade in osteosarcoma There is an urgent need for new therapeutic approaches in OS and this study represents an important preclinical evaluation of a potential new treatment Several of the experiments and conclusions based on them caught our attention and raised questions that were not addressed either in the main text nor supplemental information Firstly the authors claim to demonstrate that osteoclast specific deletion of Rank impacted on OS The authors have used Mx1 Cre to undertake these studies and treated the mice with pIpC to induce Cre activity to delete a conditional Rank allele Whilst this is a good model for somatic deletion of Rank it is not able to be interpreted as osteoclast specific nor hematopoietic restricted There are a large number of studies demonstrating that Mx1 Cre induces recombination of loxP flanked alleles very broadly in hematopoietic cells including hematopoietic stem and progenitors skeletal stem and progenitor cells that give rise to osteoblasts and would be potentially forming the OS in these models and many other tissues in the mouse See amongst a large number of studies PMID 7660125 17574022 16754850 22385654 19322176 16598206 21123947 and https www jax org strain 005673 Furthermore the induction regimen used is considerably different from that contained in previous publications using this allele We administered pIpC subcutaneously at a dosage of 300ug every third day for 13 weeks starting at 10 weeks of age Most regimens involve the administration of pIpC for 3 7 doses in total every alternate day and this has been sufficient in most cases to elicit efficient recombination of loxP flanked alleles in a range of tissues in the mouse The authors do not present any data demonstrating specific recombination only in osteoclasts derived from these mice to support their interpretation

    Original URL path: http://stm.sciencemag.org/content/7/317/317ra197.e-letters (2016-02-10)
    Open archived version from archive

  • RANKL blockade prevents and treats aggressive osteosarcomas | Science Translational Medicine
    Molyneux Princess Margaret Cancer Centre Ontario Cancer Institute University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Trevor D McKee Spatio Temporal Targeting and Amplification of Radiation Response STTARR Program University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Paul Waterhouse Princess Margaret Cancer Centre Ontario Cancer Institute University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Josef M Penninger Institute of Molecular Biotechnology of the Austrian Academy of Sciences IMBA Dr Bohr Gasse 3 1030 Vienna Austria Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rama Khokha Princess Margaret Cancer Centre Ontario Cancer Institute University Health Network 101 College Street Toronto Ontario M5G 1L7 Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Article Figures Data Info Metrics eLetters PDF This article has a correction Please see Erratum for the Research Article RANKL blockade prevents and treats aggressive osteosarcomas by Y Chen M A Di Grappa S D Molyneux T D McKee P Waterhouse J M Penninger R Khokha February 03 2016 Log in to view full text Username Enter your Sciencemag org username Password Enter the password that accompanies your username Forgot your username or password Log in Join Subscribe Purchase Article Activate Member Account Renew Subscription Recommend a subscription to your library Help for librarians Science Translational Medicine Vol 7 Issue 317 09 December 2015 Table of Contents Article Tools Email Thank you for your interest in spreading the word about Science Translational Medicine NOTE We only request your email address so that the person you are recommending the page to knows that you wanted them to see it and that it is not junk mail We do not capture any email address Your Email Your Name Send To Enter multiple addresses on separate lines or separate them with commas You are going to email the following RANKL blockade prevents and treats aggressive osteosarcomas Message Subject Your Name has forwarded a page to you from Science Translational Medicine Message Body Your Name thought you would like to see this page from the Science Translational Medicine web site Your Personal Message Send Message Download Powerpoint Print Save to my folders User Name Password Remember my user name password Submit Alerts Please log in to add an alert for this article Username Enter your Sciencemag org username Password Enter the password that accompanies your username Log in Request Permissions Citation tools RANKL blockade prevents and treats aggressive osteosarcomas By Yan Chen Marco A Di Grappa Sam D Molyneux Trevor D McKee Paul Waterhouse Josef M Penninger Rama Khokha Science

    Original URL path: http://stm.sciencemag.org/content/7/317/317ra197.full (2016-02-10)
    Open archived version from archive

  • Table of Contents — December 09, 2015, 7 (317) | Science Translational Medicine
    Ng Hans Ippel Dennis Suylen Rabea Hinkel Xavier Blanchet Fanny Gaillard Michele D Amico Phillipp von Hundelshausen Alexander Zarbock Christoph Scheiermann Tilman M Hackeng Sabine Steffens Christian Kupatt Gerry A F Nicolaes Christian Weber Oliver Soehnlein Science Translational Medicine 09 Dec 2015 317ra196 Disrupting the HNP1 and CCL5 heteromer between neutrophils and platelets blocks monocyte recruitment to inflammatory sites Editor s Summary Abstract Full Text PDF RANKL blockade prevents and treats aggressive osteosarcomas By Yan Chen Marco A Di Grappa Sam D Molyneux Trevor D McKee Paul Waterhouse Josef M Penninger Rama Khokha Science Translational Medicine 09 Dec 2015 317ra197 Denosumab an antibody targeting RANKL is effective against osteosarcoma in mouse models Editor s Summary Abstract Full Text PDF Tracking genetically engineered lymphocytes long term reveals the dynamics of T cell immunological memory By Giacomo Oliveira Eliana Ruggiero Maria Teresa Lupo Stanghellini Nicoletta Cieri Mattia D Agostino Raffaele Fronza Christina Lulay Francesca Dionisio Sara Mastaglio Raffaella Greco Jacopo Peccatori Alessandro Aiuti Alessandro Ambrosi Luca Biasco Attilio Bondanza Antonio Lambiase Catia Traversari Luca Vago Christof von Kalle Manfred Schmidt Claudio Bordignon Fabio Ciceri Chiara Bonini Science Translational Medicine 09 Dec 2015 317ra198 Antigen exposure and differentiation phenotype influence long term persistence of memory T cells after hematopoietic stem cell transplant Editor s Summary Abstract Full Text PDF Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imaging By Ingo Stoffels Stefan Morscher Iris Helfrich Uwe Hillen Julia Leyh Neal C Burton Thomas C P Sardella Jing Claussen Thorsten D Poeppel Hagen S Bachmann Alexander Roesch Klaus Griewank Dirk Schadendorf Matthias Gunzer Joachim Klode Science Translational Medicine 09 Dec 2015 317ra199 Optoacoustic imaging strategies can be used to identify metastasis in excised lymph nodes and to determine SLN status in patients noninvasively Editor s Summary Abstract Full Text PDF Editors Choice Pecking order By Pamela Bhatti Science Translational Medicine 09 Dec 2015 317ec210 Pigeons distinguish clinically relevant features on breast screening pathology slides but not x ray images Full Text Press pause to fast forward By Biju Parekkadan Science Translational Medicine 09 Dec 2015 317ec211 A novel RNA based device controlling key proteins can effectively and reversibly arrest human cell cycles Full Text CREBBP mutated cancers HAT tricked By Anish Thomas Science Translational Medicine 09 Dec 2015 317ec212 CREBBP deficient cancer cells are profoundly addicted to EP300 and MYC plays a key role in this interaction Full Text Letters Comment on One health one literature Weaving together veterinary and medical research By K C Kent Lloyd Colin McKerlie Je Kyung Seong Frauke Neff Science Translational Medicine 09 Dec 2015 317le3 The research community can have confidence in data from well executed phenotyping projects Abstract Full Text PDF Response to comment on One health one literature Weaving together veterinary and medical research By Mary M Christopher Science Translational Medicine 09 Dec 2015 317lr3 Comparative knowledge is essential for effective preclinical translational research Abstract Full Text PDF More From Science Translational Medicine Current Table of Contents Archive In the Pipeline

    Original URL path: http://stm.sciencemag.org/content/7/317 (2016-02-10)
    Open archived version from archive

  • Table of Contents — December 09, 2015, 7 (317) | Science Translational Medicine
    Judy Ng Hans Ippel Dennis Suylen Rabea Hinkel Xavier Blanchet Fanny Gaillard Michele D Amico Phillipp von Hundelshausen Alexander Zarbock Christoph Scheiermann Tilman M Hackeng Sabine Steffens Christian Kupatt Gerry A F Nicolaes Christian Weber Oliver Soehnlein Science Translational Medicine 09 Dec 2015 317ra196 Disrupting the HNP1 and CCL5 heteromer between neutrophils and platelets blocks monocyte recruitment to inflammatory sites Editor s Summary Abstract Full Text PDF RANKL blockade prevents and treats aggressive osteosarcomas By Yan Chen Marco A Di Grappa Sam D Molyneux Trevor D McKee Paul Waterhouse Josef M Penninger Rama Khokha Science Translational Medicine 09 Dec 2015 317ra197 Denosumab an antibody targeting RANKL is effective against osteosarcoma in mouse models Editor s Summary Abstract Full Text PDF Tracking genetically engineered lymphocytes long term reveals the dynamics of T cell immunological memory By Giacomo Oliveira Eliana Ruggiero Maria Teresa Lupo Stanghellini Nicoletta Cieri Mattia D Agostino Raffaele Fronza Christina Lulay Francesca Dionisio Sara Mastaglio Raffaella Greco Jacopo Peccatori Alessandro Aiuti Alessandro Ambrosi Luca Biasco Attilio Bondanza Antonio Lambiase Catia Traversari Luca Vago Christof von Kalle Manfred Schmidt Claudio Bordignon Fabio Ciceri Chiara Bonini Science Translational Medicine 09 Dec 2015 317ra198 Antigen exposure and differentiation phenotype influence long term persistence of memory T cells after hematopoietic stem cell transplant Editor s Summary Abstract Full Text PDF Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imaging By Ingo Stoffels Stefan Morscher Iris Helfrich Uwe Hillen Julia Leyh Neal C Burton Thomas C P Sardella Jing Claussen Thorsten D Poeppel Hagen S Bachmann Alexander Roesch Klaus Griewank Dirk Schadendorf Matthias Gunzer Joachim Klode Science Translational Medicine 09 Dec 2015 317ra199 Optoacoustic imaging strategies can be used to identify metastasis in excised lymph nodes and to determine SLN status in patients noninvasively Editor s Summary Abstract Full Text PDF Editors Choice Pecking order By Pamela Bhatti Science Translational Medicine 09 Dec 2015 317ec210 Pigeons distinguish clinically relevant features on breast screening pathology slides but not x ray images Full Text Press pause to fast forward By Biju Parekkadan Science Translational Medicine 09 Dec 2015 317ec211 A novel RNA based device controlling key proteins can effectively and reversibly arrest human cell cycles Full Text CREBBP mutated cancers HAT tricked By Anish Thomas Science Translational Medicine 09 Dec 2015 317ec212 CREBBP deficient cancer cells are profoundly addicted to EP300 and MYC plays a key role in this interaction Full Text Letters Comment on One health one literature Weaving together veterinary and medical research By K C Kent Lloyd Colin McKerlie Je Kyung Seong Frauke Neff Science Translational Medicine 09 Dec 2015 317le3 The research community can have confidence in data from well executed phenotyping projects Abstract Full Text PDF Response to comment on One health one literature Weaving together veterinary and medical research By Mary M Christopher Science Translational Medicine 09 Dec 2015 317lr3 Comparative knowledge is essential for effective preclinical translational research Abstract Full Text PDF More From Science Translational Medicine Current Table of Contents Archive In the

    Original URL path: http://stm.sciencemag.org/content/7/317.toc (2016-02-10)
    Open archived version from archive


  • the role of receptor activator of nuclear factor κB ligand RANKL signaling in the progression of this disease The authors also showed that denosumab an antibody against RANKL that is already used in patients with some bone diseases is effective in mouse models of osteosarcoma and is a viable candidate for future testing in human patients Osteosarcoma OS is the most common primary bone cancer which occurs primarily in children and adolescents severely affecting survivors quality of life Despite its chemosensitivity and treatment advances long term survival rates for OS patients have stagnated over the last 20 years Thus it is necessary to develop new molecularly targeted therapies for this metastatic bone cancer Mutations in TP53 and RB are linked to OS predisposition and to the evolution of spontaneous OS We established receptor activator of nuclear factor κB ligand RANKL as a therapeutic target for suppression and prevention of OS Combined conditional osteoblast specific deletions of Rb p53 and the protein kinase A PKA regulatory subunit Prkar1α genes in genetically engineered mouse models GEMMs generate aggressive osteosarcomas characterized by PKA RANKL and osteoclast hyperactivity Whole body Rankl deletion completely abrogates tumorigenesis Although osteoblastic Rank deletion has little effect osteoclastic Rank

    Original URL path: http://stm.sciencemag.org/highwire/citation/199153/medlars (2016-02-10)
    Open archived version from archive


  • models to dissect the role of receptor activator of nuclear factor κB ligand RANKL signaling in the progression of this disease The authors also showed that denosumab an antibody against RANKL that is already used in patients with some bone diseases is effective in mouse models of osteosarcoma and is a viable candidate for future testing in human patients Osteosarcoma OS is the most common primary bone cancer which occurs primarily in children and adolescents severely affecting survivors quality of life Despite its chemosensitivity and treatment advances long term survival rates for OS patients have stagnated over the last 20 years Thus it is necessary to develop new molecularly targeted therapies for this metastatic bone cancer Mutations in TP53 and RB are linked to OS predisposition and to the evolution of spontaneous OS We established receptor activator of nuclear factor κB ligand RANKL as a therapeutic target for suppression and prevention of OS Combined conditional osteoblast specific deletions of Rb p53 and the protein kinase A PKA regulatory subunit Prkar1α genes in genetically engineered mouse models GEMMs generate aggressive osteosarcomas characterized by PKA RANKL and osteoclast hyperactivity Whole body Rankl deletion completely abrogates tumorigenesis Although osteoblastic Rank deletion has little

    Original URL path: http://stm.sciencemag.org/highwire/citation/199153/refworks (2016-02-10)
    Open archived version from archive



  •