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Combination of a third generation bisphosphonate and replication-competent adenoviruses augments the cytotoxicity on mesothelioma

Overview of attention for article published in BMC Cancer, July 2016
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Title
Combination of a third generation bisphosphonate and replication-competent adenoviruses augments the cytotoxicity on mesothelioma
Published in
BMC Cancer, July 2016
DOI 10.1186/s12885-016-2483-y
Pubmed ID
Authors

Yuanyuan Jiang, Boya Zhong, Kiyoko Kawamura, Takao Morinaga, Masato Shingyoji, Ikuo Sekine, Yuji Tada, Koichiro Tatsumi, Hideaki Shimada, Kenzo Hiroshima, Masatoshi Tagawa

Abstract

Approximately 80 % of mesothelioma specimens have the wild-type p53 gene, whereas they contain homozygous deletions in the INK4A/ARF locus that encodes p14 (ARF) and the 16 (INK4A) genes. Consequently, the majority of mesothelioma is defective of the p53 pathways. We examined whether zoledronic acid (ZOL), a third generation bisphosphonate, and adenoviruses with a deletion of the E1B-55kD gene (Ad-delE1B55), which augments p53 levels in the infected tumors, could produce combinatory anti-tumor effects on human mesothelioma cells bearing the wild-type p53 gene. Cytotoxicity of ZOL and Ad-delE1B55 was assessed with a WST assay. Cell cycle changes were tested with flow cytometry. Expression levels of relevant molecules were examined with western blot analysis to investigate a possible mechanism of cytotoxicity. Furthermore, the expressions of Ad receptors on target cells and infectivity were estimated with flow cytometry. Viral replication was assayed with the tissue culture infection dose method. A combinatory use of ZOL and Ad-delE1B55 suppressed cell growth and increased sub-G1 or S-phase populations compared with a single agent, depending on cells tested. The combinatory treatment up-regulated p53 levels and subsequently enhanced the cleavage of caspase-3, 8, 9 and poly (ADP-ribose) polymerase, but expression of molecules involved in autophagy pathways were inconsistent. ZOL-treated cells also increased Ad infectivity with a dose-dependent manner and augmented Ad replication although the expression levels of integrin molecules, one of the Ad receptors, were down-regulated. These findings indicated that ZOL and Ad-delE1B55 achieved combinatory anti-tumor effects through augmented apoptotic pathways or increased viral replication.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 5 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 5 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 2 40%
Other 1 20%
Student > Bachelor 1 20%
Unspecified 1 20%
Readers by discipline Count As %
Unspecified 1 20%
Agricultural and Biological Sciences 1 20%
Immunology and Microbiology 1 20%
Neuroscience 1 20%
Medicine and Dentistry 1 20%
Other 0 0%

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 July 2016.
All research outputs
#6,129,620
of 8,071,125 outputs
Outputs from BMC Cancer
#2,228
of 3,440 outputs
Outputs of similar age
#182,221
of 258,661 outputs
Outputs of similar age from BMC Cancer
#136
of 238 outputs
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