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Therapeutic potential of antiviral drugs targeting chemorefractory colorectal adenocarcinoma cells overexpressing endogenous retroviral elements

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, August 2015
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3 tweeters

Citations

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20 Dimensions

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52 Mendeley
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Title
Therapeutic potential of antiviral drugs targeting chemorefractory colorectal adenocarcinoma cells overexpressing endogenous retroviral elements
Published in
Journal of Experimental & Clinical Cancer Research, August 2015
DOI 10.1186/s13046-015-0199-5
Pubmed ID
Authors

David Díaz-Carballo, Ali Haydar Acikelli, Jacqueline Klein, Holger Jastrow, Philipp Dammann, Thomas Wyganowski, Cihan Guemues, Sebastian Gustmann, Walter Bardenheuer, Sascha Malak, Nora Sophia Tefett, Veria Khosrawipour, Urs Giger-Pabst, Andrea Tannapfel, Dirk Strumberg

Abstract

Endoretroviruses account for circa 8 % of all transposable elements found in the genome of humans and other animals. They represent a genetic footprint of ancestral germ-cell infections of exoviruses that is transmittable to the progeny by Mendelian segregation. Traces of human endogenous retroviruses are physiologically expressed in ovarial, testicular and placental tissues as well as in stem cells. In addition, a number of these fossil viral elements have also been related to carcinogenesis. However, a relation between endoretroviruses expression and chemoresistance has not been reported yet. Twenty colorectal carcinoma patient samples were scrutinized for HERV-WE1 and HERV-FRD1 endoretroviruses using immunohistochemical approaches. In order to search for differential expression of these elements in chemotherapy refractory cells, a resistant HCT8 colon carcinoma subline was developed by serial etoposide exposure. Endoretroviral elements were detected by immunocytochemical staining, qPCR and ELISA. IC50-values of antiviral and cytostatic drugs in HCT8 cells were determined by MTT proliferation assay. The antivirals-cytostatics interaction was evaluated by the isobologram method. In this work, we show for the first time that HERV-WE1, HERV-FRD1, HERV-31, and HERV-V1 are a) simultaneously expressed in treatment-naïve colon carcinoma cells and b) upregulated after cytostatic exposure, suggesting that these retroviral elements are intimately related to chemotherapy resistance. We found a number of antiviral drugs to have cytotoxic activity and the ability to force the downregulation of HERV proteins in vitro. We also demonstrate that the use of different antiviral compounds alone or in combination with anticancer agents results in a synergistic antiproliferative effect and downregulation of different endoretroviral elements in highly chemotherapy-resistant colorectal tumor cells. Enhanced HERV-expression is associated with chemoresistance in colon carcinomas which can be overcome by antiviral drugs alone or in combination with anticancer drugs. Therefore, the introduction of antiviral compounds to the current chemotherapy regimens potentially improves patient outcomes.

Twitter Demographics

The data shown below were collected from the profiles of 3 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 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Iran, Islamic Republic of 1 2%
Unknown 51 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 12 23%
Student > Master 10 19%
Student > Bachelor 8 15%
Student > Ph. D. Student 7 13%
Student > Postgraduate 3 6%
Other 4 8%
Unknown 8 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 19 37%
Medicine and Dentistry 10 19%
Agricultural and Biological Sciences 6 12%
Immunology and Microbiology 5 10%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 2 4%
Unknown 9 17%

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 14 April 2016.
All research outputs
#3,900,353
of 7,551,260 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#121
of 397 outputs
Outputs of similar age
#119,227
of 225,963 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#6
of 24 outputs
Altmetric has tracked 7,551,260 research outputs across all sources so far. This one is in the 27th percentile – i.e., 27% of other outputs scored the same or lower than it.
So far Altmetric has tracked 397 research outputs from this source. They receive a mean Attention Score of 1.5. This one has gotten more attention than average, scoring higher than 54% 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 225,963 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 24 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.