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Vascular-targeted TNFα and IFNγ inhibits orthotopic colorectal tumor growth

Overview of attention for article published in Journal of Translational Medicine, June 2016
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Title
Vascular-targeted TNFα and IFNγ inhibits orthotopic colorectal tumor growth
Published in
Journal of Translational Medicine, June 2016
DOI 10.1186/s12967-016-0944-3
Pubmed ID
Authors

Jing Shen, Zhi Jie Li, Long Fei Li, Lan Lu, Zhan Gang Xiao, William Ka Kei Wu, Lin Zhang, Ming Xing Li, Wei Hu, Kam Ming Chan, Chi Hin Cho

Abstract

Tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) were originally identified to show potent anti-tumor activity and immunomodulatory capability. Unfortunately, several clinical studies of relevant cancer therapy did not observe significant response in maximum tolerated dose whether given alone or in combination. We have identified a tumor vasculature homing peptide (TCP-1 peptide) which targets only the vasculature of colorectal tumors but not normal blood vessels in animals and humans. In the current study, the antitumor effect of TCP-1/TNFα and TCP-1/IFNγ alone or in combination was studied in orthotopic colorectal tumor model. TCP-1/TNFα and TCP-1/IFNγ recombinant proteins were prepared and i.v. injected to study the in vivo anticancer effect in orthotopic colorectal tumor model. Tumor apoptosis was determined by TUNEL staining and cleaved caspase-3 immunofluorescent staining. Tumor infiltrating lymphocytes were analyzed by immunofluorescent staining and flow cytometry. Western-blot was performed to examine the expression of proteins. Cell apoptosis was measured by Annexin V/PI flow cytometry. Targeted delivery of TNFα or IFNγ by TCP-1 peptide exhibited better antitumor activity than unconjugated format by inducing more tumor apoptosis and also enhancing antitumor immunity shown by increased infiltration of T lymphocytes inside the tumor. More importantly, combination therapy of TCP-1/TNFα and TCP-1/IFNγ synergistically suppressed tumor growth and alleviated systematic toxicity associated with untargeted therapy. This combination therapy induced massive apoptosis/secondary necrosis in the tumor. Taken together, our data demonstrate TCP-1 is an efficient drug carrier for targeted therapy of colorectal cancer (CRC). TCP-1/TNFα combined with TCP-1/IFNγ is a promising combination therapy for CRC.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 24%
Other 4 24%
Student > Ph. D. Student 2 12%
Librarian 1 6%
Researcher 1 6%
Other 0 0%
Unknown 5 29%
Readers by discipline Count As %
Medicine and Dentistry 3 18%
Biochemistry, Genetics and Molecular Biology 2 12%
Immunology and Microbiology 2 12%
Psychology 1 6%
Pharmacology, Toxicology and Pharmaceutical Science 1 6%
Other 2 12%
Unknown 6 35%
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 27 June 2016.
All research outputs
#15,379,002
of 22,879,161 outputs
Outputs from Journal of Translational Medicine
#2,238
of 4,004 outputs
Outputs of similar age
#223,171
of 352,727 outputs
Outputs of similar age from Journal of Translational Medicine
#69
of 110 outputs
Altmetric has tracked 22,879,161 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,004 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.5. This one is in the 31st percentile – i.e., 31% 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 352,727 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 110 others from the same source and published within six weeks on either side of this one. This one is in the 7th percentile – i.e., 7% of its contemporaries scored the same or lower than it.