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Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity

Overview of attention for article published in Journal of Translational Medicine, February 2016
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Title
Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity
Published in
Journal of Translational Medicine, February 2016
DOI 10.1186/s12967-016-0816-x
Pubmed ID
Authors

Giuseppe Roscilli, Claudia De Vitis, Fabiana Fosca Ferrara, Alessia Noto, Emanuela Cherubini, Alberto Ricci, Salvatore Mariotta, Enrico Giarnieri, Maria Rosaria Giovagnoli, Maria Rosaria Torrisi, Francesca Bergantino, Susan Costantini, Francesca Fenizia, Matilde Lambiase, Luigi Aurisicchio, Nicola Normanno, Gennaro Ciliberto, Rita Mancini

Abstract

Lung cancer is the leading cause of cancer related deaths and Malignant Pleural Effusion (MPE) is a frequent complication. Current therapies suffer from lack of efficacy in a great percentage of cases, especially when cancer is diagnosed at a late stage. Moreover patients' responses vary and the outcome is unpredictable. Therefore, the identification of patients who will benefit most of chemotherapy treatment is important for accurate prognostication and better outcome. In this study, using malignant pleural effusions (MPE) from non-small cell lung cancer (NSCLC) patients, we established a collection of patient-derived Adenocarcinoma cultures which were characterized for their sensitivity to chemotherapeutic drugs used in the clinical practice. Tumor cells present in MPEs of patients with NSCLC were isolated by density gradient centrifugation, placed in culture and genotyped by next generation sequencing. In a subset of cases patient derived xenografts (PDX) were obtained upon tumor cell inoculation in rag2/IL2 knock-out mice. Isolated primary cultures were characterized and tested for drug sensitivity by in vitro proliferation assays. Additivity, antagonism or synergy for combinatorial treatments were determined by analysis with the Calcusyn software. We have optimized isolation procedures and culture conditions to expand in vitro primary cultures from Malignant Pleural Effusions (MPEs) of patients affected by lung adenocarcinomas, the most frequent form of non small cell lung cancer. Using this approach we have been able to establish 16 primary cultures from MPEs. Cells were banked at low passages and were characterized for their mutational pattern by next generation sequencing for most common driver mutations in lung cancer. Moreover, amplified cultures were shown to engraft with high efficiency when injected in immunocompromised mice. Cancer cell sensitivity to drugs used in standard chemotherapy regimens was assessed either individually or in combination. Differential chemosensitivity and different mutation profiles were observed which suggests that this isolation method could provide a platform for predicting the efficacy of chemotherapy in the clinical setting. Most importantly for six patients it was possible to establish a correlation between drug response in vitro and response to therapy in the clinic. Results obtained using primary cultured cells from MPEs underscore the heterogeneity of NSCLC in advanced stage as indicated by drug response and mutation profile. Comparison of data obtained from in vitro assays with patients' responses to therapy leads to the conclusion that this strategy may provide a potentially useful approach for evaluating individual chemosensitivity profile and tailor the therapy accordingly. Furthermore, combining MPE-derived primary cultures with their genomic testing allows to identify patients eligible to trials with novel targeted agents.

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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.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 73 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Malaysia 1 1%
United States 1 1%
Italy 1 1%
Unknown 70 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 18%
Student > Ph. D. Student 10 14%
Student > Bachelor 8 11%
Student > Master 7 10%
Student > Postgraduate 3 4%
Other 9 12%
Unknown 23 32%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 18%
Medicine and Dentistry 12 16%
Agricultural and Biological Sciences 7 10%
Engineering 3 4%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Other 10 14%
Unknown 25 34%
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 02 March 2016.
All research outputs
#15,362,070
of 22,852,911 outputs
Outputs from Journal of Translational Medicine
#2,236
of 3,999 outputs
Outputs of similar age
#176,523
of 297,594 outputs
Outputs of similar age from Journal of Translational Medicine
#40
of 75 outputs
Altmetric has tracked 22,852,911 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 3,999 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 297,594 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 75 others from the same source and published within six weeks on either side of this one. This one is in the 8th percentile – i.e., 8% of its contemporaries scored the same or lower than it.