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  • SPACECRAFT DESIGN, TESTING AND PERFORMANCE  (5)
  • Apoptosis/drug effects  (1)
  • Drug Resistance, Neoplasm/*drug effects  (1)
  • 1
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    Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-01-28
    Description: Inhibition of the BRAF(V600E) oncoprotein by the small-molecule drug PLX4032 (vemurafenib) is highly effective in the treatment of melanoma. However, colon cancer patients harbouring the same BRAF(V600E) oncogenic lesion have poor prognosis and show only a very limited response to this drug. To investigate the cause of the limited therapeutic effect of PLX4032 in BRAF(V600E) mutant colon tumours, here we performed an RNA-interference-based genetic screen in human cells to search for kinases whose knockdown synergizes with BRAF(V600E) inhibition. We report that blockade of the epidermal growth factor receptor (EGFR) shows strong synergy with BRAF(V600E) inhibition. We find in multiple BRAF(V600E) mutant colon cancers that inhibition of EGFR by the antibody drug cetuximab or the small-molecule drugs gefitinib or erlotinib is strongly synergistic with BRAF(V600E) inhibition, both in vitro and in vivo. Mechanistically, we find that BRAF(V600E) inhibition causes a rapid feedback activation of EGFR, which supports continued proliferation in the presence of BRAF(V600E) inhibition. Melanoma cells express low levels of EGFR and are therefore not subject to this feedback activation. Consistent with this, we find that ectopic expression of EGFR in melanoma cells is sufficient to cause resistance to PLX4032. Our data suggest that BRAF(V600E) mutant colon cancers (approximately 8-10% of all colon cancers), for which there are currently no targeted treatment options available, might benefit from combination therapy consisting of BRAF and EGFR inhibitors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prahallad, Anirudh -- Sun, Chong -- Huang, Sidong -- Di Nicolantonio, Federica -- Salazar, Ramon -- Zecchin, Davide -- Beijersbergen, Roderick L -- Bardelli, Alberto -- Bernards, Rene -- England -- Nature. 2012 Jan 26;483(7387):100-3. doi: 10.1038/nature10868.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Carcinogenesis, Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22281684" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/pharmacology/therapeutic use ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cetuximab ; Colorectal Neoplasms/*drug therapy/*enzymology/genetics/pathology ; Drug Resistance, Neoplasm/*drug effects ; Drug Synergism ; Enzyme Activation/drug effects ; Erlotinib Hydrochloride ; Feedback, Physiological/*drug effects ; Female ; HEK293 Cells ; Humans ; Indoles/pharmacology/therapeutic use ; Melanoma/drug therapy/metabolism ; Mice ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Proto-Oncogene Proteins B-raf/*antagonists & ; inhibitors/chemistry/*genetics/metabolism ; Quinazolines/pharmacology/therapeutic use ; RNA Interference ; Receptor, Epidermal Growth Factor/*agonists/antagonists & inhibitors/metabolism ; Sulfonamides/pharmacology/therapeutic use ; Xenograft Model Antitumor Assays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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    PAPER CURRENT
  • 2
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    System test and flight results from infrared astronomical satellite external thermal subsystem (1985)
    In:  Other Sources
    Details
    Publication Date: 2011-08-19
    Description: The Infrared Astronomical Satellite (IRAS) received its system level thermal testing in a solar simulator in September and October 1982 and was launched in January 1983. In order to reduce costs and meet a tight launch schedule, a system thermal test approach was employed which combined the goals of thermal design development tests, thermal balance tests, and thermal vacuum qualification tests. This approach relied heavily on the use of a computer-controlled automatic data handling and heater control system which reduced reliance on human monitoring of test data in comparison to past projects. The validity of this approach has been borne out by flight results. During the whole mission most temperatures were within the desired range and close to predictions. Included under the external thermal subsystem are room temperature electronics and radiatively cooled surfaces with temperatures below 100 and 200K.
    Keywords: SPACECRAFT DESIGN, TESTING AND PERFORMANCE
    Type: Journal of Spacecraft and Rockets (ISSN 0022-4650); 22; 166-169
    Format: text
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    NASA TECHNICAL REPORTS
  • 3
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    A small solar electric ion propulsion spacecraft for lunar science (1988)
    In:  Other Sources
    Details
    Publication Date: 2019-06-28
    Description: A lightweight spacecraft design concept has been developed which employs solar-electric ion propulsion to conduct a lunar science mission. The design relies on off-the-shelf technology to achieve high reliability and near-term launch readiness status. Overall project costs are kept to a minimum through the concentration of mission objectives, as well as through the minimization of payload launch costs by resort to the Space Shuttle's Get-Away Special canister. Attention is given to the spacecraft's instrumentation configuration.
    Keywords: SPACECRAFT DESIGN, TESTING AND PERFORMANCE
    Type: AIAA PAPER 88-2836
    Format: text
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    NASA TECHNICAL REPORTS
  • 4
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    Lunar Get Away Special (GAS) spacecraft (1987)
    In:  Other Sources
    Details
    Publication Date: 2019-06-28
    Description: A new approach to the resumption of Lunar missions is discussed which relies upon Shuttle Get-Away-Special Canisters for launch and solar electric ion propulsion for slow orbit transfer to low Lunar orbit. The technique of orbit transfer is outlined along with a summary of a mission profile for a first mission which could carry a Gamma Ray Spectrometer. System design constraints are discussed followed by a description of the low mass spacecraft concept which has been developed. Particular emphasis is placed upon describing the small solar electric, xenon ion propulsion system.
    Keywords: SPACECRAFT DESIGN, TESTING AND PERFORMANCE
    Type: AIAA PAPER 87-1051
    Format: text
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    NASA TECHNICAL REPORTS
  • 5
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    A study of central cryogenic cooling system for the comet rendezvous spacecraft (1981)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: Several science instruments required temperatures between 100 K and 120 K on a proposed Halley Flyby, Tempel-2 Rendezvous Mission. Significant features of the thermal environment are a large variation in heliocentric as well as comet distance, very large solar panels for a Solar Electric Propulsion stage, and the comet dust environment. The best cooling is achieved by one central radiative cooler connected by insulated cryogenic heat pipes to the instruments. The conceptual design is of a single-stage rectangular shielded radiator deployed on a boom some distance from the spacecraft bus and solar panels. Thermal modeling determined sensitivity to solar and comet distance and was used to optimize cooler geometry.
    Keywords: SPACECRAFT DESIGN, TESTING AND PERFORMANCE
    Type: AIAA PAPER 81-1099 , Thermophysics Conference; Jun 23, 1981 - Jun 25, 1981; Palo Alto, CA
    Format: text
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    NASA TECHNICAL REPORTS
  • 6
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    An approach to the design of a simple, radiation hard, highly integrated and reliable, lightweight satellite bus (1988)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: A spacecraft system concept has been developed which uses ion propulsion and a small, simple, lightweight design approach to carry out a focused lunar science mission. The design relies on existing technology to achieve high reliability and the possibility of a near-term launch. Key characteristics of the mission are highly focused objectives, low launch costs, minimization of development risks and design simplicity. The spacecraft for the lunar mission is described with particular emphasis on the design and reliability approaches used. The degree of adaptability of this basic class of spacecraft bus is discussed with particular emphasis on its application as a technology testbed vehicle. Several potential mission applications are reviewed.
    Keywords: SPACECRAFT DESIGN, TESTING AND PERFORMANCE
    Type: AIAA/DARPA Meeting on Lightweight Satellite Systems; Aug 04, 1987 - Aug 06, 1987; Monterey, CA; United States
    Format: text
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    NASA TECHNICAL REPORTS
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