Publications by authors named "A Grevot"
The replacement of a proportion of concurrent controls by virtual controls in nonclinical safety studies has gained traction over the last few years. This is supported by foundational work, encouraged by regulators, and aligned with societal expectations regarding the use of animals in research. This paper provides an overview of the points to consider for any institution on the verge of implementing this concept, with emphasis given on database creation, risks, and discipline-specific perspectives.
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- The YAP/Hippo pathway regulates organ growth and helps maintain stem cell function, with LATS kinases playing a critical role by inactivating YAP.
- A new small-molecule inhibitor, NIBR-LTSi, has been developed that selectively targets LATS kinases, activating YAP signaling and promoting tissue regeneration in laboratory settings.
- While NIBR-LTSi shows promise by enhancing liver regeneration and supporting stem cell characteristics, prolonged use may lead to excessive cell proliferation and dedifferentiation, which could limit its therapeutic benefits.
Article Synopsis
- A lot of new ideas have been created in the last 10 years to help reduce the use of animals in testing new medicines, with a cool new idea called Virtual Control Groups (VCGs).
- The paper talks about the challenges of using VCGs, especially in studying body tissues, and mentions that scientists and regulators need to work together to make this happen smoothly.
- They suggest that to prove VCGs really work, tests should be done with both VCGs and standard control groups at the same time, and later they could even replace the use of real animals in some cases!
Historical data from control groups in animal toxicity studies are currently mainly used for comparative purposes to assess validity and robustness of study results. Due to the highly controlled environment in which the studies are performed and the homogeneity of the animal collectives it has been proposed to use the historical data to build so-called virtual control groups, which could partly or entirely replace the concurrent control group. This would constitute a substantial contribution to the reduction of animal use in safety studies.
View Article and Find Full Text PDFInhibitors of double minute 2 protein (MDM2)-tumor protein 53 (TP53) interaction are predicted to be effective in tumors in which the gene is wild type, by preventing TP53 protein degradation. One such setting is represented by the frequent deletion in human cancer that, through inactivation of , activates MDM2 protein, which in turn degrades TP53 tumor suppressor. Here we used piggyBac (PB) transposon insertional mutagenesis to anticipate resistance mechanisms occurring during treatment with the MDM2-TP53 inhibitor HDM201.
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