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  • 2005-2009  (408)
  • 1
    Publication Date: 2006
    Keywords: Seismology ; Attenuation ; Strong motions ; Earthquake hazard ; Spectrum ; Site amplification ; Horizontal to vertical spectral ratio ; Nakamura ; Micro-tremor (seismic noise) ; BSSA
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  • 2
    Publication Date: 2006
    Keywords: Seismology ; Attenuation ; Strong motions ; Earthquake hazard ; Spectrum ; Site amplification ; BSSA
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  • 3
    Publication Date: 2008-10-25
    Description: Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694412/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694412/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Li -- Getz, Gad -- Wheeler, David A -- Mardis, Elaine R -- McLellan, Michael D -- Cibulskis, Kristian -- Sougnez, Carrie -- Greulich, Heidi -- Muzny, Donna M -- Morgan, Margaret B -- Fulton, Lucinda -- Fulton, Robert S -- Zhang, Qunyuan -- Wendl, Michael C -- Lawrence, Michael S -- Larson, David E -- Chen, Ken -- Dooling, David J -- Sabo, Aniko -- Hawes, Alicia C -- Shen, Hua -- Jhangiani, Shalini N -- Lewis, Lora R -- Hall, Otis -- Zhu, Yiming -- Mathew, Tittu -- Ren, Yanru -- Yao, Jiqiang -- Scherer, Steven E -- Clerc, Kerstin -- Metcalf, Ginger A -- Ng, Brian -- Milosavljevic, Aleksandar -- Gonzalez-Garay, Manuel L -- Osborne, John R -- Meyer, Rick -- Shi, Xiaoqi -- Tang, Yuzhu -- Koboldt, Daniel C -- Lin, Ling -- Abbott, Rachel -- Miner, Tracie L -- Pohl, Craig -- Fewell, Ginger -- Haipek, Carrie -- Schmidt, Heather -- Dunford-Shore, Brian H -- Kraja, Aldi -- Crosby, Seth D -- Sawyer, Christopher S -- Vickery, Tammi -- Sander, Sacha -- Robinson, Jody -- Winckler, Wendy -- Baldwin, Jennifer -- Chirieac, Lucian R -- Dutt, Amit -- Fennell, Tim -- Hanna, Megan -- Johnson, Bruce E -- Onofrio, Robert C -- Thomas, Roman K -- Tonon, Giovanni -- Weir, Barbara A -- Zhao, Xiaojun -- Ziaugra, Liuda -- Zody, Michael C -- Giordano, Thomas -- Orringer, Mark B -- Roth, Jack A -- Spitz, Margaret R -- Wistuba, Ignacio I -- Ozenberger, Bradley -- Good, Peter J -- Chang, Andrew C -- Beer, David G -- Watson, Mark A -- Ladanyi, Marc -- Broderick, Stephen -- Yoshizawa, Akihiko -- Travis, William D -- Pao, William -- Province, Michael A -- Weinstock, George M -- Varmus, Harold E -- Gabriel, Stacey B -- Lander, Eric S -- Gibbs, Richard A -- Meyerson, Matthew -- Wilson, Richard K -- P50 CA070907/CA/NCI NIH HHS/ -- R01 CA154365/CA/NCI NIH HHS/ -- U19 CA084953/CA/NCI NIH HHS/ -- U19 CA084953-050003/CA/NCI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- U54 HG003067-04/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- England -- Nature. 2008 Oct 23;455(7216):1069-75. doi: 10.1038/nature07423.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Genome Center at Washington University, Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948947" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma, Bronchiolo-Alveolar/*genetics ; Female ; Gene Dosage ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Lung Neoplasms/*genetics ; Male ; Mutation/*genetics ; Proto-Oncogenes/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2008-09-19
    Description: The pseudogap region of the phase diagram is an important unsolved puzzle in the field of high-transition-temperature (high-T(c)) superconductivity, characterized by anomalous physical properties. There are open questions about the number of distinct phases and the possible presence of a quantum-critical point underneath the superconducting dome. The picture has remained unclear because there has not been conclusive evidence for a new type of order. Neutron scattering measurements for YBa(2)Cu(3)O(6+delta) (YBCO) resulted in contradictory claims of no and weak magnetic order, and the interpretation of muon spin relaxation measurements on YBCO and of circularly polarized photoemission experiments on Bi(2)Sr(2)CaCu(2)O(8+delta)(refs 12, 13) has been controversial. Here we use polarized neutron diffraction to demonstrate for the model superconductor HgBa(2)CuO(4+delta) (Hg1201) that the characteristic temperature T* marks the onset of an unusual magnetic order. Together with recent results for YBCO, this observation constitutes a demonstration of the universal existence of such a state. The findings appear to rule out theories that regard T* as a crossover temperature rather than a phase transition temperature. Instead, they are consistent with a variant of previously proposed charge-current-loop order that involves apical oxygen orbitals, and with the notion that many of the unusual properties arise from the presence of a quantum-critical point.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Y -- Baledent, V -- Barisic, N -- Cho, Y -- Fauque, B -- Sidis, Y -- Yu, G -- Zhao, X -- Bourges, P -- Greven, M -- England -- Nature. 2008 Sep 18;455(7211):372-5. doi: 10.1038/nature07251.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18800135" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2009-11-27
    Description: Protein design provides a rigorous test of our knowledge about proteins and allows the creation of novel enzymes for biotechnological applications. Whereas progress has been made in designing proteins that mimic native proteins structurally, it is more difficult to design functional proteins. In comparison to recent successes in designing non-metalloproteins, it is even more challenging to rationally design metalloproteins that reproduce both the structure and function of native metalloenzymes. This is because protein metal-binding sites are much more varied than non-metal-containing sites, in terms of different metal ion oxidation states, preferred geometry and metal ion ligand donor sets. Because of their variability, it has been difficult to predict metal-binding site properties in silico, as many of the parameters, such as force fields, are ill-defined. Therefore, the successful design of a structural and functional metalloprotein would greatly advance the field of protein design and our understanding of enzymes. Here we report a successful, rational design of a structural and functional model of a metalloprotein, nitric oxide reductase (NOR), by introducing three histidines and one glutamate, predicted as ligands in the active site of NOR, into the distal pocket of myoglobin. A crystal structure of the designed protein confirms that the minimized computer model contains a haem/non-haem Fe(B) centre that is remarkably similar to that in the crystal structure. This designed protein also exhibits NO reduction activity, and so models both the structure and function of NOR, offering insight that the active site glutamate is required for both iron binding and activity. These results show that structural and functional metalloproteins can be rationally designed in silico.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297211/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297211/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yeung, Natasha -- Lin, Ying-Wu -- Gao, Yi-Gui -- Zhao, Xuan -- Russell, Brandy S -- Lei, Lanyu -- Miner, Kyle D -- Robinson, Howard -- Lu, Yi -- GM062211/GM/NIGMS NIH HHS/ -- R01 GM062211/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Dec 24;462(7276):1079-82. doi: 10.1038/nature08620. Epub 2009 Nov 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940850" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallization ; Iron/metabolism ; Models, Molecular ; Myoglobin/chemistry ; Nitric Oxide/metabolism ; Oxidoreductases/*chemical synthesis/*chemistry/metabolism ; Protein Binding ; Protein Structure, Tertiary
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  • 6
    Publication Date: 2008-12-05
    Description: Stem cells reside in a specialized, regulatory environment termed the niche that dictates how they generate, maintain and repair tissues. We have previously documented that transplanted haematopoietic stem and progenitor cell populations localize to subdomains of bone-marrow microvessels where the chemokine CXCL12 is particularly abundant. Using a combination of high-resolution confocal microscopy and two-photon video imaging of individual haematopoietic cells in the calvarium bone marrow of living mice over time, we examine the relationship of haematopoietic stem and progenitor cells to blood vessels, osteoblasts and endosteal surface as they home and engraft in irradiated and c-Kit-receptor-deficient recipient mice. Osteoblasts were enmeshed in microvessels and relative positioning of stem/progenitor cells within this complex tissue was nonrandom and dynamic. Both cell autonomous and non-autonomous factors influenced primitive cell localization. Different haematopoietic cell subsets localized to distinct locations according to the stage of differentiation. When physiological challenges drove either engraftment or expansion, bone-marrow stem/progenitor cells assumed positions in close proximity to bone and osteoblasts. Our analysis permits observing in real time, at a single cell level, processes that previously have been studied only by their long-term outcome at the organismal level.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820276/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820276/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lo Celso, Cristina -- Fleming, Heather E -- Wu, Juwell W -- Zhao, Cher X -- Miake-Lye, Sam -- Fujisaki, Joji -- Cote, Daniel -- Rowe, David W -- Lin, Charles P -- Scadden, David T -- R01 EY014106/EY/NEI NIH HHS/ -- R01 EY014106-05/EY/NEI NIH HHS/ -- England -- Nature. 2009 Jan 1;457(7225):92-6. doi: 10.1038/nature07434. Epub 2008 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052546" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Vessels/cytology ; Bone Marrow ; Cell Division ; Cell Separation ; Hematopoietic Stem Cells/*cytology ; Mice ; Mice, Inbred C57BL ; Osteoblasts/cytology ; Proto-Oncogene Proteins c-kit/genetics/metabolism ; Skull/cytology ; Stem Cell Niche/*cytology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2009-12-25
    Description: The inference of transcriptional networks that regulate transitions into physiological or pathological cellular states remains a central challenge in systems biology. A mesenchymal phenotype is the hallmark of tumour aggressiveness in human malignant glioma, but the regulatory programs responsible for implementing the associated molecular signature are largely unknown. Here we show that reverse-engineering and an unbiased interrogation of a glioma-specific regulatory network reveal the transcriptional module that activates expression of mesenchymal genes in malignant glioma. Two transcription factors (C/EBPbeta and STAT3) emerge as synergistic initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBPbeta and STAT3 reprograms neural stem cells along the aberrant mesenchymal lineage, whereas elimination of the two factors in glioma cells leads to collapse of the mesenchymal signature and reduces tumour aggressiveness. In human glioma, expression of C/EBPbeta and STAT3 correlates with mesenchymal differentiation and predicts poor clinical outcome. These results show that the activation of a small regulatory module is necessary and sufficient to initiate and maintain an aberrant phenotypic state in cancer cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011561/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011561/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carro, Maria Stella -- Lim, Wei Keat -- Alvarez, Mariano Javier -- Bollo, Robert J -- Zhao, Xudong -- Snyder, Evan Y -- Sulman, Erik P -- Anne, Sandrine L -- Doetsch, Fiona -- Colman, Howard -- Lasorella, Anna -- Aldape, Ken -- Califano, Andrea -- Iavarone, Antonio -- 1RC2CA148308-01/CA/NCI NIH HHS/ -- P20 GM075059/GM/NIGMS NIH HHS/ -- P20GM075059/GM/NIGMS NIH HHS/ -- R01 CA085628/CA/NCI NIH HHS/ -- R01 CA101644/CA/NCI NIH HHS/ -- R01 CA109755/CA/NCI NIH HHS/ -- R01 CA127643/CA/NCI NIH HHS/ -- R01 NS061776/NS/NINDS NIH HHS/ -- R01 NS061776-01A2/NS/NINDS NIH HHS/ -- R01 NS061776-02/NS/NINDS NIH HHS/ -- R01CA085628/CA/NCI NIH HHS/ -- R01CA101644/CA/NCI NIH HHS/ -- R01CA109755/CA/NCI NIH HHS/ -- R01NS061776/NS/NINDS NIH HHS/ -- RC2 CA148308/CA/NCI NIH HHS/ -- U01 CA168426/CA/NCI NIH HHS/ -- U54 CA121852/CA/NCI NIH HHS/ -- U54CA121852/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jan 21;463(7279):318-25. doi: 10.1038/nature08712. Epub 2009 Dec 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20032975" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Neoplasms/diagnosis/*genetics/*pathology ; CCAAT-Enhancer-Binding Protein-beta/genetics/metabolism ; Cell Differentiation/genetics ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/metabolism/pathology ; Cellular Reprogramming/genetics ; Computational Biology ; *Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Glioma/diagnosis/genetics/pathology ; Humans ; Mesenchymal Stromal Cells/metabolism/pathology ; Mesoderm/*metabolism/*pathology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Invasiveness/genetics/pathology ; Neurons/metabolism/pathology ; Prognosis ; Reproducibility of Results ; STAT3 Transcription Factor/genetics/metabolism ; *Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2005-09-10
    Description: On 4 July 2005, many observatories around the world and in space observed the collision of Deep Impact with comet 9P/Tempel 1 or its aftermath. This was an unprecedented coordinated observational campaign. These data show that (i) there was new material after impact that was compositionally different from that seen before impact; (ii) the ratio of dust mass to gas mass in the ejecta was much larger than before impact; (iii) the new activity did not last more than a few days, and by 9 July the comet's behavior was indistinguishable from its pre-impact behavior; and (iv) there were interesting transient phenomena that may be correlated with cratering physics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meech, K J -- Ageorges, N -- A'Hearn, M F -- Arpigny, C -- Ates, A -- Aycock, J -- Bagnulo, S -- Bailey, J -- Barber, R -- Barrera, L -- Barrena, R -- Bauer, J M -- Belton, M J S -- Bensch, F -- Bhattacharya, B -- Biver, N -- Blake, G -- Bockelee-Morvan, D -- Boehnhardt, H -- Bonev, B P -- Bonev, T -- Buie, M W -- Burton, M G -- Butner, H M -- Cabanac, R -- Campbell, R -- Campins, H -- Capria, M T -- Carroll, T -- Chaffee, F -- Charnley, S B -- Cleis, R -- Coates, A -- Cochran, A -- Colom, P -- Conrad, A -- Coulson, I M -- Crovisier, J -- deBuizer, J -- Dekany, R -- de Leon, J -- Dello Russo, N -- Delsanti, A -- DiSanti, M -- Drummond, J -- Dundon, L -- Etzel, P B -- Farnham, T L -- Feldman, P -- Fernandez, Y R -- Filipovic, M D -- Fisher, S -- Fitzsimmons, A -- Fong, D -- Fugate, R -- Fujiwara, H -- Fujiyoshi, T -- Furusho, R -- Fuse, T -- Gibb, E -- Groussin, O -- Gulkis, S -- Gurwell, M -- Hadamcik, E -- Hainaut, O -- Harker, D -- Harrington, D -- Harwit, M -- Hasegawa, S -- Hergenrother, C W -- Hirst, P -- Hodapp, K -- Honda, M -- Howell, E S -- Hutsemekers, D -- Iono, D -- Ip, W-H -- Jackson, W -- Jehin, E -- Jiang, Z J -- Jones, G H -- Jones, P A -- Kadono, T -- Kamath, U W -- Kaufl, H U -- Kasuga, T -- Kawakita, H -- Kelley, M S -- Kerber, F -- Kidger, M -- Kinoshita, D -- Knight, M -- Lara, L -- Larson, S M -- Lederer, S -- Lee, C-F -- Levasseur-Regourd, A C -- Li, J Y -- Li, Q-S -- Licandro, J -- Lin, Z-Y -- Lisse, C M -- LoCurto, G -- Lovell, A J -- Lowry, S C -- Lyke, J -- Lynch, D -- Ma, J -- Magee-Sauer, K -- Maheswar, G -- Manfroid, J -- Marco, O -- Martin, P -- Melnick, G -- Miller, S -- Miyata, T -- Moriarty-Schieven, G H -- Moskovitz, N -- Mueller, B E A -- Mumma, M J -- Muneer, S -- Neufeld, D A -- Ootsubo, T -- Osip, D -- Pandea, S K -- Pantin, E -- Paterno-Mahler, R -- Patten, B -- Penprase, B E -- Peck, A -- Petitas, G -- Pinilla-Alonso, N -- Pittichova, J -- Pompei, E -- Prabhu, T P -- Qi, C -- Rao, R -- Rauer, H -- Reitsema, H -- Rodgers, S D -- Rodriguez, P -- Ruane, R -- Ruch, G -- Rujopakarn, W -- Sahu, D K -- Sako, S -- Sakon, I -- Samarasinha, N -- Sarkissian, J M -- Saviane, I -- Schirmer, M -- Schultz, P -- Schulz, R -- Seitzer, P -- Sekiguchi, T -- Selman, F -- Serra-Ricart, M -- Sharp, R -- Snell, R L -- Snodgrass, C -- Stallard, T -- Stecklein, G -- Sterken, C -- Stuwe, J A -- Sugita, S -- Sumner, M -- Suntzeff, N -- Swaters, R -- Takakuwa, S -- Takato, N -- Thomas-Osip, J -- Thompson, E -- Tokunaga, A T -- Tozzi, G P -- Tran, H -- Troy, M -- Trujillo, C -- Van Cleve, J -- Vasundhara, R -- Vazquez, R -- Vilas, F -- Villanueva, G -- von Braun, K -- Vora, P -- Wainscoat, R J -- Walsh, K -- Watanabe, J -- Weaver, H A -- Weaver, W -- Weiler, M -- Weissman, P R -- Welsh, W F -- Wilner, D -- Wolk, S -- Womack, M -- Wooden, D -- Woodney, L M -- Woodward, C -- Wu, Z-Y -- Wu, J-H -- Yamashita, T -- Yang, B -- Yang, Y-B -- Yokogawa, S -- Zook, A C -- Zauderer, A -- Zhao, X -- Zhou, X -- Zucconi, J-M -- New York, N.Y. -- Science. 2005 Oct 14;310(5746):265-9. Epub 2005 Sep 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Astronomy, University of Hawaii at Manoa, 2680 Woodlawn Drive, Honolulu, HI 96822, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16150977" target="_blank"〉PubMed〈/a〉
    Keywords: Cosmic Dust ; Jupiter ; *Meteoroids ; Organic Chemicals ; Photometry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2007-04-28
    Description: The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Engelman, Jeffrey A -- Zejnullahu, Kreshnik -- Mitsudomi, Tetsuya -- Song, Youngchul -- Hyland, Courtney -- Park, Joon Oh -- Lindeman, Neal -- Gale, Christopher-Michael -- Zhao, Xiaojun -- Christensen, James -- Kosaka, Takayuki -- Holmes, Alison J -- Rogers, Andrew M -- Cappuzzo, Federico -- Mok, Tony -- Lee, Charles -- Johnson, Bruce E -- Cantley, Lewis C -- Janne, Pasi A -- 1K12CA87723-01/CA/NCI NIH HHS/ -- GM41890/GM/NIGMS NIH HHS/ -- K08CA120060-01/CA/NCI NIH HHS/ -- P01 CA089021/CA/NCI NIH HHS/ -- P20CA90578-02/CA/NCI NIH HHS/ -- R01 GM041890/GM/NIGMS NIH HHS/ -- R01-CA111560/CA/NCI NIH HHS/ -- R01CA114465-01/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 May 18;316(5827):1039-43. Epub 2007 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463250" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; CHO Cells ; Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cricetinae ; Cricetulus ; Drug Resistance, Neoplasm ; Enzyme Inhibitors ; *Gene Amplification ; Humans ; Indoles/pharmacology ; Lung Neoplasms/drug therapy/genetics/metabolism/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Proto-Oncogene Proteins/*genetics/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-met ; Quinazolines/*pharmacology/therapeutic use ; Receptor, ErbB-3/*metabolism ; Receptors, Growth Factor/*genetics/metabolism ; *Signal Transduction ; Sulfones/pharmacology
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-11-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sooby, Jane -- Zhao, Xin -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):523. doi: 10.1126/science.326_523.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19900883" target="_blank"〉PubMed〈/a〉
    Keywords: Food, Organic/*analysis/standards ; *Nutritive Value
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