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Comparative drug pa...
Comparative drug pair screening across multiple glioblastoma cell lines reveals novel drug-drug interactions
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Schmidt, L. (author)
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Kling, T. (author)
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Monsefi, N. (author)
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Olsson, M. (author)
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Hansson, C. (author)
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- Baskaran, Sathishkumar (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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- Lundgren, Bo (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)
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- Martens, Ulf (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)
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- Häggblad, Maria (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)
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- Westermark, Bengt (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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- Nilsson, Karin Forsberg (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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- Uhrbom, Lene (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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Karlsson-Lindahl, L. (author)
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- Gerlee, Philip, 1980 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematik,Department of Mathematical Sciences, Mathematics,Chalmers tekniska högskola,Chalmers University of Technology,University of Gothenburg
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- Nelander, Sven (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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(creator_code:org_t)
- 2013-10-06
- 2013
- English.
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In: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 15:11, s. 1469-1478
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Abstract
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- Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults, and despite state-of-the-art treatment, survival remains poor and novel therapeutics are sorely needed. The aim of the present study was to identify new synergistic drug pairs for GBM. In addition, we aimed to explore differences in drug-drug interactions across multiple GBM-derived cell cultures and predict such differences by use of transcriptional biomarkers. We performed a screen in which we quantified drug-drug interactions for 465 drug pairs in each of the 5 GBM cell lines U87MG, U343MG, U373MG, A172, and T98G. Selected interactions were further tested using isobole-based analysis and validated in 5 glioma-initiating cell cultures. Furthermore, drug interactions were predicted using microarray-based transcriptional profiling in combination with statistical modeling. Of the 5 465 drug pairs, we could define a subset of drug pairs with strong interaction in both standard cell lines and glioma-initiating cell cultures. In particular, a subset of pairs involving the pharmaceutical compounds rimcazole, sertraline, pterostilbene, and gefitinib showed a strong interaction in a majority of the cell cultures tested. Statistical modeling of microarray and interaction data using sparse canonical correlation analysis revealed several predictive biomarkers, which we propose could be of importance in regulating drug pair responses. We identify novel candidate drug pairs for GBM and suggest possibilities to prospectively use transcriptional biomarkers to predict drug interactions in individual cases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- drug combination responses
- glioblastoma therapy
- glioblastoma stem cell
- cultures
- predictive medicine
- antidepressant sertraline
- tumor
- gene
- classification
- therapeutics
- temozolomide
- combination
- progression
- carcinoma
- apoptosis
- tumor
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Schmidt, L.
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Kling, T.
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Monsefi, N.
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Olsson, M.
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Hansson, C.
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Baskaran, Sathis ...
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show more...
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Lundgren, Bo
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Martens, Ulf
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Häggblad, Maria
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Westermark, Beng ...
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Nilsson, Karin F ...
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Uhrbom, Lene
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Karlsson-Lindahl ...
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Gerlee, Philip, ...
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Nelander, Sven
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
- Articles in the publication
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Neuro-Oncology
- By the university
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University of Gothenburg
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Chalmers University of Technology
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Stockholm University
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Uppsala University