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A look inside the mechanistic black box: Are red blood cells the critical effectors of RRx-001 cytotoxicity?

Overview of attention for article published in Medical Oncology, May 2016
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Title
A look inside the mechanistic black box: Are red blood cells the critical effectors of RRx-001 cytotoxicity?
Published in
Medical Oncology, May 2016
DOI 10.1007/s12032-016-0775-3
Pubmed ID
Authors

Pedro Cabrales, Jan Scicinski, Tony Reid, Frans Kuypers, Sandra Larkin, Marcel Fens, Arnold Oronsky, Bryan Oronsky

Abstract

The therapeutic potential of epi-immunotherapeutic anticancer agent RRx-001 in cancer has been validated with preclinical and clinical studies, since RRx-001 has successfully completed a phase 1 trial and multiple single-agent and combination phase 2 trials with preliminary evidence of promising activity are underway. Previous experimental work has implicated diverse anticancer mechanisms such as oxidative stress, ATP and NADPH depletion, anti-angiogenesis and epigenetic modulation in the overall antitumor effect of RRx-001. The hypothesis of this study was that the RRx-001 red blood cells are the essential and de facto intermediaries responsible for the reprograming of tumor behavior via transfer of their intracellular and membrane contents. To test this hypothesis, and thereby resolve the "black box" incompleteness in the continuity of the mechanism, the fate of red blood cells incubated with RRx-001 was explored in vitro and in vivo both in healthy animals and in tumor-bearing mice. The collective results establish that RRx-001-derivatized red blood cells are the critical "missing links" to explain the specificity and anticancer activity of RRx-001, including its immunomodulatory effects on tumor-associated macrophages. These experimental results delineate a novel erythrocyte-based mechanism without precedent in the annals of oncology and open the door to rational combination strategies with RRx-001 both in cancer therapy and beyond, particularly in disease states that affect red blood cell and vascular function such as malaria, leishmaniasis, sickle-cell disease and hemorrhagic shock.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 38%
Professor 2 15%
Student > Bachelor 2 15%
Unspecified 2 15%
Researcher 1 8%
Other 1 8%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 2 15%
Unspecified 2 15%
Psychology 2 15%
Agricultural and Biological Sciences 2 15%
Economics, Econometrics and Finance 1 8%
Other 4 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 28 May 2016.
All research outputs
#10,392,081
of 13,029,986 outputs
Outputs from Medical Oncology
#422
of 754 outputs
Outputs of similar age
#184,356
of 265,309 outputs
Outputs of similar age from Medical Oncology
#10
of 28 outputs
Altmetric has tracked 13,029,986 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 754 research outputs from this source. They receive a mean Attention Score of 2.7. This one is in the 29th percentile – i.e., 29% of its peers scored the same or lower than it.
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 265,309 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.