| Title |
A clinical protocol to inhibit the HGF/c-Met pathway for malignant mesothelioma with an intrapleural injection of adenoviruses expressing the NK4 gene
|
|---|---|
| Published in |
SpringerPlus, July 2015
|
| DOI | 10.1186/s40064-015-1123-3 |
| Pubmed ID | |
| Authors |
Yuji Tada, Kenzo Hiroshima, Hideaki Shimada, Naoya Morishita, Toshiro Shirakawa, Kunio Matsumoto, Masato Shingyoji, Ikuo Sekine, Koichiro Tatsumi, Masatoshi Tagawa |
| Abstract |
The hepatocyte growth factor (HGF)/c-Met signal pathway is up-regulated in human mesothelioma and suppression of the HGF/c-Met signaling with a competitive inhibitor, NK4 homologous to HGF in the structure, produced anti-tumor effects to mesothelioma in a preclinical study. Mesothelioma is highly resistant to a number of chemotherapeutic agents but distant metastasis to extra-thoracic organs is relatively infrequent until the late stage. We planned to conduct a clinical study of gene therapy with adenoviruses expressing the NK4 gene (Ad-NK4) to control the local tumor growth. The study is designed to inject Ad-NK4 into the intrapleural cavity with a dose escalation manner from 10(10) to 10(12) virus particles per patient and to examine safety and possible clinical benefits. The clinical investigation is a first-in-human trial to use the NK4 gene and to block the HGF/c-Met pathway with gene medicine. We conducted in vivo animal experiments to examine the safety level as one of the preclinical studies, and showed that Ad DNA administered in the pleural cavity was detected in many parenchymal organs. Biochemical and pathological analyses showed that liver damages were the major adverse effects with little toxicity to other organs. These studies firstly demonstrated biodistribution and transgene expression after an intrapleural injection of Ad vectors in an animal study, which contrasts with an intravenous injection showing relatively rapid clearance of Ad-NK4. The clinical study can also provide information regarding production of NK4 protein and antibody against NK4, and inhibition levels of the HGF/c-Met pathway by detecting dephosphorylation of c-Met in mesothelioma cells. These data will be crucial to judge whether local production of NK4 molecules can be an anti-cancer strategy. UMIN clinical trials registry, Japan. Register ID: UMIN15771. |
Mendeley readers
The data shown below were compiled from readership statistics for 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 15 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 33% |
| Student > Bachelor | 2 | 13% |
| Student > Doctoral Student | 1 | 7% |
| Professor | 1 | 7% |
| Professor > Associate Professor | 1 | 7% |
| Other | 0 | 0% |
| Unknown | 5 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 2 | 13% |
| Medicine and Dentistry | 2 | 13% |
| Agricultural and Biological Sciences | 2 | 13% |
| Chemical Engineering | 1 | 7% |
| Mathematics | 1 | 7% |
| Other | 2 | 13% |
| Unknown | 5 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 19. 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 13 August 2015.
All research outputs
#1,622,219
of 22,821,814 outputs
Outputs from SpringerPlus
#88
of 1,851 outputs
Outputs of similar age
#22,094
of 262,375 outputs
Outputs of similar age from SpringerPlus
#5
of 112 outputs
Altmetric has tracked 22,821,814 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,851 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one has done particularly well, scoring higher than 95% 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 262,375 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 91% of its contemporaries.
We're also able to compare this research output to 112 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 95% of its contemporaries.