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Attention Score in Context
| Title |
Combination of lutetium-177 labelled anti-L1CAM antibody chCE7 with the clinically relevant protein kinase inhibitor MK1775: a novel combination against human ovarian carcinoma
|
|---|---|
| Published in |
BMC Cancer, September 2018
|
| DOI | 10.1186/s12885-018-4836-1 |
| Pubmed ID | |
| Authors |
Dennis Lindenblatt, Nastassja Terraneo, Giovanni Pellegrini, Susan Cohrs, Philipp René Spycher, David Vukovic, Martin Béhé, Roger Schibli, Jürgen Grünberg |
| Abstract |
Protein kinase inhibitors (PKIs) are currently tested in clinical studies (phase I-III) as an alternative strategy against (recurrent) ovarian cancer. Besides their anti-tumour efficacy, several PKIs have also shown radiosensitizing effects when combined with external beam radiation. Based on these results we asked if the addition of PKIs offers a therapeutic opportunity to improve radioimmunotherapy (RIT) against ovarian cancer. Five PKIs (alisertib, MK1775, MK2206, saracatinib, temsirolimus) were chosen for cytotoxicity screenings based on their current clinical trials in the treatment of ovarian cancer and their influence on cell cycle regulation and DNA damage repair pathways. We combined selected PKIs with 177Lu-labelled anti-L1CAM monoclonal antibody chCE7 for our investigations. PKIs cytotoxicity was determined via cell colony-forming assays. Biomarker of DNA double-strand breaks (DSBs, γH2A.X) was analysed by western blot and fluorescence microscopy. Flow cytometric measurements were performed to evaluate levels of apoptosis based on mono- or combination treatments. The best combination was used for in vivo combination therapy studies in nude mice with SKOV3ip and IGROV1 human ovarian cancer xenografts. Bonferroni correction was used to determine statistical significance for multiple comparisons. The highest cytotoxicity against both cell lines was observed for MK1775 and alisertib. Combinations including 177Lu-labelled mAb chCE7 and MK1775 decreased 177Lu-DOTA-chCE7 IC60-values 14-fold, compared to 6-fold, when the radioimmunoconjugate was combined with alisertib. The most effective PKI MK1775 was further evaluated and demonstrated synergistic effects in combination with 177Lu-DOTA-chCE7 against IGROV1 cells. Significantly higher amounts of DSBs were detected in IGROV1 cells after combination (91%) compared to either treatment alone (MK1775: 52%; radioimmunoconjugate: 72%; p < 0.0125). Early-apoptosis was significantly enhanced in IGROV1 cells correlating with induced DSBs (177Lu-DOTA-chCE7: 8%, MK1775: 28%, 177Lu-DOTA-chCE7 + MK1775: 40%, p < 0.0125). Immunohistochemistry analysis of γH2A.X expression levels after therapy in SKOV3ip xenografts revealed a high sensitivity of the tumour cells to MK1775 and a high radioresistance. A prominent effect of tumour growth inhibition of the RIT and of the combination therapy was observed in vivo in a late stage IGROV1 xenograft model. Our results warrant further evaluation of combination of MK1775 and radioimmunotherapy. |
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% |
| Student > Ph. D. Student | 3 | 12% |
| Student > Bachelor | 2 | 8% |
| Other | 2 | 8% |
| Other | 1 | 4% |
| Unknown | 9 | 35% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 5 | 19% |
| Medicine and Dentistry | 4 | 15% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 8% |
| Unspecified | 1 | 4% |
| Mathematics | 1 | 4% |
| Other | 4 | 15% |
| 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 14 December 2022.
All research outputs
#6,595,160
of 23,332,901 outputs
Outputs from BMC Cancer
#1,697
of 8,446 outputs
Outputs of similar age
#117,824
of 341,710 outputs
Outputs of similar age from BMC Cancer
#34
of 159 outputs
Altmetric has tracked 23,332,901 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 8,446 research outputs from this source. They receive a mean Attention Score of 4.4. This one has done well, scoring higher than 78% 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 341,710 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 64% of its contemporaries.
We're also able to compare this research output to 159 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.