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Combination statin and chemotherapy inhibits proliferation and cytotoxicity of an aggressive natural killer cell leukemia

Overview of attention for article published in Biomarker Research, August 2018
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3 X users

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31 Mendeley
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Title
Combination statin and chemotherapy inhibits proliferation and cytotoxicity of an aggressive natural killer cell leukemia
Published in
Biomarker Research, August 2018
DOI 10.1186/s40364-018-0140-0
Pubmed ID
Authors

Austin B. Henslee, Timothy A. Steele

Abstract

Aggressive natural killer cell leukemia is a devastating disease, with an average patient survival time of less than 2 months following diagnosis. Due to P-glycoprotein-mediated resistance of the tumor cells most forms of chemotherapy are of limited efficacy, therefore new treatment strategies are needed. Statin drugs have recently been found to inhibit the growth of various tumor cell types. We investigated the effects of statin drug-mediated mevalonate pathway inhibition on cell proliferation, tumor-induced cytotoxicity, cell cycle progression and ERK MAP kinase signal transduction pathway activation. Flow cytometry was used to perform the cytotoxicity and cell cycle analyses and Western blotting was used to investigate ERK MAP kinase activation. Statistical significance was assessed by Student's t-test. Fluvastatin and atorvastatin were found to inhibit cell growth and tumor-induced cytotoxicity. These effects were reversed by the addition of mevalonate, signifying that the impact of the drugs were on the mevalonate pathway. Both drugs affected cell cycle progression by causing a significant increase in the percentage of cells in the G0/G1 phase and a reduction in the S phase and the G2/M phases of the cell cycle. Low concentrations of statin drugs were able to abrogate ERK MAP kinase pathway activation, which is typically constitutively activated in aggressive natural killer cell leukemias and important in tumor-mediated cytotoxicity. Addition of statins to chemotherapy caused enhanced inhibition of cell growth and cytotoxicity, compared to either agent alone; a combination therapy that could conceivably benefit some patients. These investigations suggest that inhibiting the mevalonate pathway might provide a more effective therapy against this deadly disease when combined with chemotherapy. Given that millions of people are currently taking statin drugs to lower cholesterol levels, the risk profile for statin drugs and their side effects are well-known. Our studies suggest that it may be beneficial to explore statin-chemotherapy combination in the treatment of aggressive natural killer cell leukemias.

X Demographics

X Demographics

The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 13%
Professor > Associate Professor 4 13%
Student > Doctoral Student 3 10%
Student > Bachelor 3 10%
Student > Ph. D. Student 3 10%
Other 5 16%
Unknown 9 29%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 5 16%
Biochemistry, Genetics and Molecular Biology 4 13%
Medicine and Dentistry 3 10%
Nursing and Health Professions 2 6%
Agricultural and Biological Sciences 2 6%
Other 2 6%
Unknown 13 42%
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 27 October 2022.
All research outputs
#15,815,423
of 25,483,400 outputs
Outputs from Biomarker Research
#173
of 387 outputs
Outputs of similar age
#190,484
of 341,614 outputs
Outputs of similar age from Biomarker Research
#3
of 5 outputs
Altmetric has tracked 25,483,400 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 387 research outputs from this source. They receive a mean Attention Score of 5.0. This one has gotten more attention than average, scoring higher than 53% 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 341,614 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 5 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.