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Starving cancer from the outside and inside: separate and combined effects of calorie restriction and autophagy inhibition on Ras-driven tumors

Overview of attention for article published in Cancer & Metabolism, September 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (78th percentile)

Mentioned by

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9 tweeters
facebook
5 Facebook pages

Citations

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23 Dimensions

Readers on

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58 Mendeley
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Title
Starving cancer from the outside and inside: separate and combined effects of calorie restriction and autophagy inhibition on Ras-driven tumors
Published in
Cancer & Metabolism, September 2016
DOI 10.1186/s40170-016-0158-4
Pubmed ID
Authors

Laura M. Lashinger, Ciara H. O’Flanagan, Sarah M. Dunlap, Audrey J. Rasmussen, Shannon Sweeney, Jessie Yangxiang Guo, Alessia Lodi, Stefano Tiziani, Eileen White, Stephen D. Hursting

Abstract

Calorie restriction (CR) prevents obesity and exerts anticancer effects in many preclinical models. CR is also increasingly being used in cancer patients as a sensitizing strategy prior to chemotherapy regimens. While the beneficial effects of CR are widely accepted, the mechanisms through which CR affects tumor growth are incompletely understood. In many cell types, CR and other nutrient stressors can induce autophagy, which provides energy and metabolic substrates critical for cancer cell survival. We hypothesized that limiting extracellular and intracellular substrate availability by combining CR with autophagy inhibition would reduce tumor growth more effectively than either treatment alone. A 30 % CR diet, relative to control diet, in nude mice resulted in significant decreases in body fat, blood glucose, and serum insulin, insulin-like growth factor-1, and leptin levels concurrent with increased adiponectin levels. In a xenograft model in nude mice involving H-Ras(G12V)-transformed immortal baby mouse kidney epithelial cells with (Atg5 (+/+) ) and without (Atg5 (-/-)) autophagic capacity, the CR diet (relative to control diet) genetically induced autophagy inhibition and their combination, each reduced tumor development and growth. Final tumor volume was greatest for Atg5 (+/+) tumors in control-fed mice, intermediate for Atg5 (+/+) tumors in CR-fed mice and Atg5 (-/-) tumors in control-fed mice, and lowest for Atg5 (-/-) tumors in CR mice. In Atg5 (+/+) tumors, autophagic flux was increased in CR-fed relative to control-fed mice, suggesting that the prosurvival effects of autophagy induction may mitigate the tumor suppressive effects of CR. Metabolomic analyses of CR-fed, relative to control-fed, nude mice showed significant decreases in circulating glucose and amino acids and significant increases in ketones, indicating CR induced negative energy balance. Combining glucose deprivation with autophagy deficiency in Atg5 (-/-) cells resulted in significantly reduced in vitro colony formation relative to glucose deprivation or autophagy deficiency alone. Combined restriction of extracellular (via CR in vivo or glucose deprivation in vitro) and intracellular (via autophagy inhibition) sources of energy and nutrients suppresses Ras-driven tumor growth more effectively than either CR or autophagy deficiency alone. Interventions targeting both systemic energy balance and tumor-cell intrinsic autophagy may represent a novel and effective anticancer strategy.

Twitter Demographics

The data shown below were collected from the profiles of 9 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 58 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Canada 1 2%
Unknown 57 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 22%
Student > Ph. D. Student 11 19%
Student > Master 7 12%
Student > Doctoral Student 4 7%
Student > Bachelor 4 7%
Other 7 12%
Unknown 12 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 24%
Medicine and Dentistry 11 19%
Agricultural and Biological Sciences 9 16%
Pharmacology, Toxicology and Pharmaceutical Science 5 9%
Immunology and Microbiology 1 2%
Other 5 9%
Unknown 13 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 11 August 2017.
All research outputs
#1,670,287
of 11,598,144 outputs
Outputs from Cancer & Metabolism
#22
of 94 outputs
Outputs of similar age
#55,581
of 260,581 outputs
Outputs of similar age from Cancer & Metabolism
#1
of 4 outputs
Altmetric has tracked 11,598,144 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 94 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one has done well, scoring higher than 76% 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 260,581 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 78% of its contemporaries.
We're also able to compare this research output to 4 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them