| Title |
Activity of the polyamine-vectorized anti-cancer drug F14512 against pediatric glioma and neuroblastoma cell lines.
|
|---|---|
| Published in |
Investigational New Drugs, July 2014
|
| DOI | 10.1007/s10637-014-0132-3 |
| Pubmed ID | |
| Authors |
Pierre Leblond, Elodie Boulet, Christine Bal-Mahieu, Arnaud Pillon, Anna Kruczynski, Nicolas Guilbaud, Christian Bailly, Thierry Sarrazin, Eric Lartigau, Amélie Lansiaux, Samuel Meignan |
| Abstract |
The poor prognosis of children with high-grade glioma (HGG) and high-risk neuroblastoma, despite multidisciplinary therapeutic approaches, demands new treatments for these indications. F14512 is a topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells via the Polyamine Transport System (PTS) and increases topoisomerase II poisoning. Here, F14512 was evaluated in pediatric HGG and neuroblastoma cell lines. PTS activity and specificity were evaluated using a fluorescent spermine-coupled probe. The cytotoxicity of F14512, alone or in combination with ionizing radiation and chemotherapeutic agents, was investigated in vitro. The antitumor activity of F14512 was assessed in vivo using a liver-metastatic model of neuroblastoma. An active PTS was evidenced in all tested cell lines, providing a specific and rapid transfer of spermine-coupled compounds into cell nuclei. Competition experiments confirmed the essential role of PTS in the cell uptake and cytotoxicity of F14512. This cytotoxicity appeared greater in neuroblastoma cells compared with HGG cells but appeared independent of PTS activity levels. In vivo evaluation confirmed a marked and prolonged antitumoral effect in neuroblastoma cells. The combinations of F14512 with cisplatin and carboplatin were often found to be synergistic, and we demonstrated the significant radiosensitizing potential of F14512 in the MYCN-amplified Kelly cell line. Thus, F14512 appears more effective than etoposide in pediatric tumor cell lines, with greater efficacy in neuroblastoma cells compared with HGG cells. The synergistic effects observed with platinum compounds and the radiosensitizing effect could lead to a clinical development of the drug in pediatric oncology. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 26 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 19% |
| Student > Master | 4 | 15% |
| Other | 3 | 12% |
| Student > Ph. D. Student | 2 | 8% |
| Student > Postgraduate | 2 | 8% |
| Other | 4 | 15% |
| Unknown | 6 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 35% |
| Chemistry | 3 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 8% |
| Immunology and Microbiology | 1 | 4% |
| Social Sciences | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 9 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. 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 December 2018.
All research outputs
#6,940,930
of 22,758,248 outputs
Outputs from Investigational New Drugs
#288
of 1,168 outputs
Outputs of similar age
#66,004
of 226,417 outputs
Outputs of similar age from Investigational New Drugs
#7
of 15 outputs
Altmetric has tracked 22,758,248 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 1,168 research outputs from this source. They receive a mean Attention Score of 4.7. This one has gotten more attention than average, scoring higher than 73% 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 226,417 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 69% of its contemporaries.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.