کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2039882 1073087 2014 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Uncovering Scaling Laws to Infer Multidrug Response of Resistant Microbes and Cancer Cells
ترجمه فارسی عنوان
کشف قوانین پوسته شدن به منظور پاسخ دادن به چندین دارو از میکروب مقاوم و سلول های سرطانی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی


• A simple model describes drug-response surfaces in multiple cell types
• Responses of drug-sensitive and -resistant cells are unified by scaling laws
• Scaling laws allow prediction of two-drug responses in resistant mutants

SummaryDrug resistance in bacterial infections and cancers constitutes a major threat to human health. Treatments often include several interacting drugs, but even potent therapies can become ineffective in resistant mutants. Here, we simplify the picture of drug resistance by identifying scaling laws that unify the multidrug responses of drug-sensitive and -resistant cells. On the basis of these scaling relationships, we are able to infer the two-drug response of resistant mutants in previously unsampled regions of dosage space in clinically relevant microbes such as E. coli, E. faecalis, S. aureus, and S. cerevisiae as well as human non-small-cell lung cancer, melanoma, and breast cancer stem cells. Importantly, we find that scaling relations also apply across evolutionarily close strains. Finally, scaling allows one to rapidly identify new drug combinations and predict potent dosage regimes for targeting resistant mutants without any prior mechanistic knowledge about the specific resistance mechanism.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 6, Issue 6, 27 March 2014, Pages 1073–1084
نویسندگان
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