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Metabolic imaging using hyperpolarized 13C‐pyruvate to assess sensitivity to the B‐Raf inhibitor vemurafenib in melanoma cells and xenografts

Overview of attention for article published in Journal of Cellular and Molecular Medicine, December 2019
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Title
Metabolic imaging using hyperpolarized 13C‐pyruvate to assess sensitivity to the B‐Raf inhibitor vemurafenib in melanoma cells and xenografts
Published in
Journal of Cellular and Molecular Medicine, December 2019
DOI 10.1111/jcmm.14890
Pubmed ID
Authors

Stefania Acciardo, Lionel Mignion, Estelle Lacomblez, Céline Schoonjans, Nicolas Joudiou, Florian Gourgue, Caroline Bouzin, Jean‐François Baurain, Bernard Gallez, Bénédicte F. Jordan

Abstract

Nearly all melanoma patients with a BRAF-activating mutation will develop resistance after an initial clinical benefit from BRAF inhibition (BRAFi). The aim of this work is to evaluate whether metabolic imaging using hyperpolarized (HP) 13 C pyruvate can serve as a metabolic marker of early response to BRAFi in melanoma, by exploiting the metabolic effects of BRAFi. Mice bearing human melanoma xenografts were treated with the BRAFi vemurafenib or vehicle. In vivo HP 13 C magnetic resonance spectroscopy was performed at baseline and 24 hours after treatment to evaluate changes in pyruvate-to-lactate conversion. Oxygen partial pressure was measured via electron paramagnetic resonance oximetry. Ex vivo qRT-PCR, immunohistochemistry and WB analysis were performed on tumour samples collected at the same time-points selected for in vivo experiments. Similar approaches were applied to evaluate the effect of BRAFi on sensitive and resistant melanoma cells in vitro, excluding the role of tumour microenvironment. BRAF inhibition induced a significant increase in the HP pyruvate-to-lactate conversion in vivo, followed by a reduction of hypoxia. Conversely, the conversion was inhibited in vitro, which was consistent with BRAFi-mediated impairment of glycolysis. The paradoxical increase of pyruvate-to-lactate conversion in vivo suggests that such conversion is highly influenced by the tumour microenvironment.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Professor 2 18%
Researcher 2 18%
Student > Bachelor 1 9%
Student > Ph. D. Student 1 9%
Other 1 9%
Other 0 0%
Unknown 4 36%
Readers by discipline Count As %
Medicine and Dentistry 2 18%
Biochemistry, Genetics and Molecular Biology 1 9%
Environmental Science 1 9%
Social Sciences 1 9%
Nursing and Health Professions 1 9%
Other 0 0%
Unknown 5 45%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 December 2019.
All research outputs
#15,064,058
of 23,182,015 outputs
Outputs from Journal of Cellular and Molecular Medicine
#1,555
of 3,512 outputs
Outputs of similar age
#262,266
of 459,344 outputs
Outputs of similar age from Journal of Cellular and Molecular Medicine
#23
of 111 outputs
Altmetric has tracked 23,182,015 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,512 research outputs from this source. They receive a mean Attention Score of 3.7. This one has gotten more attention than average, scoring higher than 52% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 459,344 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 111 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 75% of its contemporaries.