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  • 1
    Lexicon Article
    Lexicon Article
    Language: English
    In: Pocket Oncology
    ISBN: 978-1-4698-7178-3
    Source: Gale Virtual Reference Library (GVRL)
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  • 2
    Language: English
    In: Clinical cancer research : an official journal of the American Association for Cancer Research, 15 June 2016, Vol.22(12), pp.2832-4
    Description: MET exon 14 alterations are a diverse group of mutations, many of which disrupt splice acceptor or donor sites leading to exon 14 skipping, impaired receptor degradation, and oncogenic transformation. These alterations are clinically targetable with MET-directed therapy. Clin Cancer Res; 22(12); 2832-4. ©2016 AACRSee related article by Tong et al., p. 3048.
    Keywords: Alternative Splicing -- Genetics ; Carcinoma, Non-Small-Cell Lung -- Genetics ; Lung Neoplasms -- Genetics ; Proto-Oncogene Proteins C-Met -- Genetics
    ISSN: 1078-0432
    E-ISSN: 15573265
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  • 3
    Language: English
    In: European Journal of Cancer, December 2016, Vol.69, pp.S138-S138
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S0959-8049(16)33010-6 Byline: A. Drilon, N. Hofmann, D. Flynn, B. Smith, M. Davare
    Keywords: Medicine
    ISSN: 0959-8049
    E-ISSN: 1879-0852
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  • 4
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 29 September 2015, Vol.112(39), pp.E5381-90
    Description: Oncogenic ROS1 fusion proteins are molecular drivers in multiple malignancies, including a subset of non-small cell lung cancer (NSCLC). The phylogenetic proximity of the ROS1 and anaplastic lymphoma kinase (ALK) catalytic domains led to the clinical repurposing of the Food and Drug Administration (FDA)-approved ALK inhibitor crizotinib as a ROS1 inhibitor. Despite the antitumor activity of crizotinib observed in both ROS1- and ALK-rearranged NSCLC patients, resistance due to acquisition of ROS1 or ALK kinase domain mutations has been observed clinically, spurring the development of second-generation inhibitors. Here, we profile the sensitivity and selectivity of seven ROS1 and/or ALK inhibitors at various levels of clinical development. In contrast to crizotinib's dual ROS1/ALK activity, cabozantinib (XL-184) and its structural analog foretinib (XL-880) demonstrate a striking selectivity for ROS1 over ALK. Molecular dynamics simulation studies reveal structural features that distinguish the ROS1 and ALK kinase domains and contribute to differences in binding site and kinase selectivity of the inhibitors tested. Cell-based resistance profiling studies demonstrate that the ROS1-selective inhibitors retain efficacy against the recently reported CD74-ROS1(G2032R) mutant whereas the dual ROS1/ALK inhibitors are ineffective. Taken together, inhibitor profiling and stringent characterization of the structure-function differences between the ROS1 and ALK kinase domains will facilitate future rational drug design for ROS1- and ALK-driven NSCLC and other malignancies.
    Keywords: Alk ; Ros1 ; Inhibitor ; Kinase ; Structural Modelling ; Models, Molecular ; Anilides -- Pharmacology ; Antineoplastic Agents -- Pharmacology ; Carcinoma, Non-Small-Cell Lung -- Drug Therapy ; Drug Resistance, Neoplasm -- Physiology ; Protein-Tyrosine Kinases -- Antagonists & Inhibitors ; Proto-Oncogene Proteins -- Antagonists & Inhibitors ; Pyridines -- Pharmacology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 5
    Language: English
    In: The Lancet Respiratory Medicine, January 2017, Vol.5(1), pp.5-6
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S2213-2600(16)30369-1 Byline: Alexander Drilon (a) Author Affiliation: (a) Thoracic Oncology Service and Developmental Therapeutics Clinic, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA
    Keywords: Medicine
    ISSN: 2213-2600
    E-ISSN: 2213-2619
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  • 6
    Article
    Article
    Language: English
    In: Journal of Thoracic Oncology, November 2017, Vol.12(11), pp.S1724-S1725
    Keywords: Medicine
    ISSN: 1556-0864
    E-ISSN: 1556-1380
    Source: ScienceDirect Journals (Elsevier)
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  • 7
    Language: English
    In: Diabetes, 05/2018, Vol.67(Supplement 1), p.923-P
    ISSN: 0012-1797
    E-ISSN: 1939-327X
    Source: CrossRef
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  • 8
    Language: English
    In: Advances in experimental medicine and biology, 2016, Vol.893, pp.155-178
    Description: KRAS-mutant lung cancers account for approximately 25% of non-small cell lung carcinomas, thus representing an enormous burden of cancer worldwide. KRAS mutations are clear drivers of tumor growth and are characterized by a complex biology involving the interaction between mutant KRAS, various growth factor pathways, and tumor suppressor genes. While KRAS mutations are classically associated with a significant smoking history, they are also identified in a substantial proportion of never-smokers. These mutations are found largely in lung adenocarcinomas with solid growth patterns and tumor-infiltrating lymphocytes. A variety of tools are available for diagnosis including Sanger sequencing, multiplex mutational hotspot profiling, and next-generation sequencing. The prognostic and predictive roles of KRAS status remain controversial. It has become increasingly clear, however, that KRAS mutations drive primary resistance to EGFR tyrosine kinase inhibition. Until recently, mutant KRAS was not thought of as a clinically-targetable driver in lung cancers. With the expansion of our knowledge regarding the biology of KRAS-mutant lung cancers and the role of MEK and PI3K/mTOR inhibition, the face of targeted therapeutics for this genomic subset of patients is slowly beginning to change.
    Keywords: Erlotinib Resistance ; Hsp90 Inhibition ; Kras Mutation ; Lung Adenocarcinoma ; Lung Cancer ; Mek Inhibition ; Pi3k Inhibition ; Selumetinib ; Targeted Therapy ; Mtor Inhibition ; Molecular Targeted Therapy ; Mutation ; Lung Neoplasms -- Genetics ; Proto-Oncogene Proteins P21(Ras) -- Genetics
    ISSN: 0065-2598
    E-ISSN: 22148019
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 9
    Language: Turkish
    In: International e-Journal of Educational Studies, 01 September 2018, Vol.2(4), pp.81-91
    Description: The education system in Kosovo is in the phase of implementing the curricular reforms which aim at changing the teaching and learning approach. The new curriculum is a necessary innovation in pre-university education system and it has already started to be implemented in all schools in Kosovo, faces many difficulties, especially in achieving learning outcomes in some curricular areas. This research aims at analyzing the obstacles and challenges in achieving results in the Languages and Communication area and to recommend appropriate ways to facilitate its implementation. The representative group consists 75 teachers who work in five primary schools in Kosovo while the data is collected through a questionnaire for teachers. The research findings show that most teachers have sufficient knowledge and have positive attitude towards new curriculum. Challenges arising from this process are: insufficient knowledge of the new curriculum, inadequate cooperation among the teachers,  lack of ICT and supporting materials in schools, difficulties in planning the learning results, and non-regular monitoring of teachers, textbook compliance with the principles and requirements of the new curriculum The development of competences and the improvement of results in this area can be achieved through changing educational policies as well as monitoring and accountability of teachers.
    Keywords: Kosovo'S New Curriculum ; Curriculum Areas ; Languages and Communication ; Learning Outcomes ; Kosovo'S New Curriculum ; Curriculum Areas ; Languages and Communication ; Learning Outcomes
    ISSN: International eJournal of Educational Studies
    E-ISSN: 2602-4241
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  • 10
    In: Applied Technologies and Innovations, 2016, Vol.12(1)
    ISSN: Applied Technologies and Innovations
    E-ISSN: 18044999
    Source: CrossRef
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