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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Preclinical Efficacy of Ado-trastuzumab Emtansine in the Brain Microenvironment
|
|---|---|
| Published in |
JNCI: Journal of the National Cancer Institute, November 2015
|
| DOI | 10.1093/jnci/djv313 |
| Pubmed ID | |
| Authors |
Vasileios Askoxylakis, Gino B Ferraro, David P Kodack, Mark Badeaux, Ram C Shankaraiah, Giorgio Seano, Jonas Kloepper, Trupti Vardam, John D Martin, Kamila Naxerova, Divya Bezwada, Xiaolong Qi, Martin K Selig, Elena Brachtel, Dan G Duda, Peigen Huang, Dai Fukumura, Jeffrey A Engelman, Rakesh K Jain |
| Abstract |
Central nervous system (CNS) metastases represent a major problem in the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer because of the disappointing efficacy of HER2-targeted therapies against brain lesions. The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) has shown efficacy in trastuzumab-resistant systemic breast cancer. Here, we tested the hypothesis that T-DM1 could overcome trastuzumab resistance in murine models of brain metastases. We treated female nude mice bearing BT474 or MDA-MB-361 brain metastases (n = 9-11 per group) or cancer cells grown in organotypic brain slice cultures with trastuzumab or T-DM1 at equivalent or equipotent doses. Using intravital imaging, molecular techniques and histological analysis we determined tumor growth, mouse survival, cancer cell apoptosis and proliferation, tumor drug distribution, and HER2 signaling. Data were analyzed with one-way analysis of variance (ANOVA), Kaplan-Meier analysis, and Coefficient of Determination. All statistical tests were two-sided. T-DM1 delayed the growth of HER2-positive breast cancer brain metastases compared with trastuzumab. These findings were consistent between HER2-driven and PI3K-driven tumors. The activity of T-DM1 resulted in a survival benefit (median survival for BT474 tumors: 28 days for trastuzumab vs 112 days for T-DM1, hazard ratio = 6.2, 95% confidence interval = 6.1 to 85.84, P < .001). No difference in drug distribution or HER2-signaling was revealed between the two groups. However, T-DM1 led to a statistically significant increase in tumor cell apoptosis (one-way ANOVA for ApopTag, P < .001), which was associated with mitotic catastrophe. T-DM1 can overcome resistance to trastuzumab therapy in HER2-driven or PI3K-driven breast cancer brain lesions due to the cytotoxicity of the DM1 component. Clinical investigation of T-DM1 for patients with CNS metastases from HER2-positive breast cancer is warranted. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Switzerland | 1 | 20% |
| United States | 1 | 20% |
| Unknown | 3 | 60% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 60% |
| Practitioners (doctors, other healthcare professionals) | 2 | 40% |
Mendeley readers
The data shown below were compiled from readership statistics for 102 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | <1% |
| United States | 1 | <1% |
| Sweden | 1 | <1% |
| France | 1 | <1% |
| Unknown | 98 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 19 | 19% |
| Researcher | 17 | 17% |
| Other | 7 | 7% |
| Student > Doctoral Student | 7 | 7% |
| Student > Bachelor | 7 | 7% |
| Other | 17 | 17% |
| Unknown | 28 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 16 | 16% |
| Medicine and Dentistry | 15 | 15% |
| Agricultural and Biological Sciences | 12 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 7% |
| Chemistry | 6 | 6% |
| Other | 14 | 14% |
| Unknown | 32 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 08 July 2020.
All research outputs
#14,677,835
of 25,604,262 outputs
Outputs from JNCI: Journal of the National Cancer Institute
#6,056
of 7,870 outputs
Outputs of similar age
#137,164
of 298,333 outputs
Outputs of similar age from JNCI: Journal of the National Cancer Institute
#77
of 128 outputs
Altmetric has tracked 25,604,262 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 7,870 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.4. This one is in the 22nd percentile – i.e., 22% 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 298,333 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 53% of its contemporaries.
We're also able to compare this research output to 128 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.