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Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy

Overview of attention for article published in BMC Cancer, March 2016
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Title
Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy
Published in
BMC Cancer, March 2016
DOI 10.1186/s12885-016-2190-8
Pubmed ID
Authors

Lihong Chang, Jiancong Huang, Kai Wang, Jingjia Li, Ruicheng Yan, Ling Zhu, Jin Ye, Xifu Wu, Shimin Zhuang, Daqing Li, Gehua Zhang

Abstract

The Mre11-Rad50-Nbs1 (MRN) complex is well known for its crucial role in initiating DNA double strand breaks (DSBs) repair pathways to resistant irradiation (IR) injury and thus facilitating radioresistance which severely reduces radiocurability of nasopharyngeal cancer (NPC). Targeting native cellular MRN function would sensitize NPC cells to IR. A recombinant adenovirus containing a mutant Rad50 gene (Ad-RAD50) expressing Rad50 zinc hook domain but lacking the ATPase domain and the Mre11 interaction domain was constructed to disrupt native cellular MRN functions. The effects of Ad-RAD50 on the MRN functions were assessed in NPC cells lines using western blot, co-immunoprecipitation and confocal microscopy analyses. The increased radiosensitivity of transient Ad-RAD50 to IR was examined in NPC cells, including MTT assay, colony formation. The molecular mechanisms of radiosensitization were confirmed by neutral comet assay and western bolts. Nude mice subcutaneous injection, tumor growth curve and TUNEL assay were used to evaluate tumor regression and apoptosis in vivo. Rad50 is remarkably upregulated in NPC cells after IR, implying the critical role of Rad50 in MRN functions. The transient expression of this mutant Rad50 decreased the levels of native cellular Rad50, Mre11 and Nbs1, weakened the interactions among these proteins, abrogated the G2/M arrest induced by DSBs and reduced the DNA repair ability in NPC cells. A combination of IR and mutant RAD50 therapy produced significant tumor cytotoxicity in vitro, with a corresponding increase in DNA damage, prevented proliferation and cell viability. Furthermore, Ad-RAD50 sensitized NPC cells to IR by causing dramatic tumor regression and inducing apoptosis in vivo. Our findings define a novel therapeutic approach to NPC radiosensitization via targeted native cellular Rad50 disruption.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 41 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 22%
Researcher 6 15%
Student > Bachelor 6 15%
Student > Doctoral Student 5 12%
Student > Master 4 10%
Other 4 10%
Unknown 7 17%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 16 39%
Medicine and Dentistry 8 20%
Agricultural and Biological Sciences 5 12%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Nursing and Health Professions 1 2%
Other 2 5%
Unknown 7 17%
Attention Score in Context

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 11 March 2016.
All research outputs
#19,292,491
of 23,881,329 outputs
Outputs from BMC Cancer
#5,591
of 8,483 outputs
Outputs of similar age
#221,468
of 301,521 outputs
Outputs of similar age from BMC Cancer
#117
of 177 outputs
Altmetric has tracked 23,881,329 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,483 research outputs from this source. They receive a mean Attention Score of 4.4. This one is in the 21st percentile – i.e., 21% 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 301,521 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 177 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.