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Efficient generation of patient-matched malignant and normal primary cell cultures from clear cell renal cell carcinoma patients: clinically relevant models for research and personalized medicine

Overview of attention for article published in BMC Cancer, July 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 (73rd percentile)
  • High Attention Score compared to outputs of the same age and source (90th percentile)

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Title
Efficient generation of patient-matched malignant and normal primary cell cultures from clear cell renal cell carcinoma patients: clinically relevant models for research and personalized medicine
Published in
BMC Cancer, July 2016
DOI 10.1186/s12885-016-2539-z
Pubmed ID
Authors

Nazleen C. Lobo, Craig Gedye, Anthony J. Apostoli, Kevin R. Brown, Joshua Paterson, Natalie Stickle, Michael Robinette, Neil Fleshner, Robert J. Hamilton, Girish Kulkarni, Alexandre Zlotta, Andrew Evans, Antonio Finelli, Jason Moffat, Michael A. S. Jewett, Laurie Ailles

Abstract

Patients with clear cell renal cell carcinoma (ccRCC) have few therapeutic options, as ccRCC is unresponsive to chemotherapy and is highly resistant to radiation. Recently targeted therapies have extended progression-free survival, but responses are variable and no significant overall survival benefit has been achieved. Commercial ccRCC cell lines are often used as model systems to develop novel therapeutic approaches, but these do not accurately recapitulate primary ccRCC tumors at the genomic and transcriptional levels. Furthermore, ccRCC exhibits significant intertumor genetic heterogeneity, and the limited cell lines available fail to represent this aspect of ccRCC. Our objective was to generate accurate preclinical in vitro models of ccRCC using tumor tissues from ccRCC patients. ccRCC primary single cell suspensions were cultured in fetal bovine serum (FBS)-containing media or defined serum-free media. Established cultures were characterized by genomic verification of mutations present in the primary tumors, expression of renal epithelial markers, and transcriptional profiling. The apparent efficiency of primary cell culture establishment was high in both culture conditions, but genotyping revealed that the majority of cultures contained normal, not cancer cells. ccRCC characteristically shows biallelic loss of the von Hippel Lindau (VHL) gene, leading to accumulation of hypoxia-inducible factor (HIF) and expression of HIF target genes. Purification of cells based on expression of carbonic anhydrase IX (CA9), a cell surface HIF target, followed by culture in FBS enabled establishment of ccRCC cell cultures with an efficiency of >80 %. Culture in serum-free conditions selected for growth of normal renal proximal tubule epithelial cells. Transcriptional profiling of ccRCC and matched normal cell cultures identified up- and down-regulated networks in ccRCC and comparison to The Cancer Genome Atlas confirmed the clinical validity of our cell cultures. The ability to establish primary cultures of ccRCC cells and matched normal kidney epithelial cells from almost every patient provides a resource for future development of novel therapies and personalized medicine for ccRCC patients.

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The data shown below were collected from the profiles of 9 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 67 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 67 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 18 27%
Student > Ph. D. Student 11 16%
Student > Bachelor 7 10%
Student > Master 5 7%
Student > Doctoral Student 4 6%
Other 9 13%
Unknown 13 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 17 25%
Agricultural and Biological Sciences 7 10%
Medicine and Dentistry 6 9%
Immunology and Microbiology 4 6%
Engineering 4 6%
Other 11 16%
Unknown 18 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 6. 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 22 January 2020.
All research outputs
#5,843,479
of 23,505,064 outputs
Outputs from BMC Cancer
#1,439
of 8,494 outputs
Outputs of similar age
#95,884
of 358,692 outputs
Outputs of similar age from BMC Cancer
#25
of 262 outputs
Altmetric has tracked 23,505,064 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 8,494 research outputs from this source. They receive a mean Attention Score of 4.4. This one has done well, scoring higher than 82% 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 358,692 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.
We're also able to compare this research output to 262 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 90% of its contemporaries.