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Establishment of patient-derived xenograft models and cell lines for malignancies of the upper gastrointestinal tract

Overview of attention for article published in Journal of Translational Medicine, April 2015
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Title
Establishment of patient-derived xenograft models and cell lines for malignancies of the upper gastrointestinal tract
Published in
Journal of Translational Medicine, April 2015
DOI 10.1186/s12967-015-0469-1
Pubmed ID
Authors

Helene Damhofer, Eva A Ebbing, Anne Steins, Lieke Welling, Johanna A Tol, Kausilia K Krishnadath, Tom van Leusden, Marc J van de Vijver, Marc G Besselink, Olivier R Busch, Mark I van Berge Henegouwen, Otto van Delden, Sybren L Meijer, Frederike Dijk, Jan Paul Medema, Hanneke W van Laarhoven, Maarten F Bijlsma

Abstract

The upper gastrointestinal tract is home to some of most notorious cancers like esophagogastric and pancreatic cancer. Several factors contribute to the lethality of these tumors, but one that stands out for both tumor types is the strong inter- as well as intratumor heterogeneity. Unfortunately, genetic tumor models do not match this heterogeneity, and for esophageal cancer no adequate genetic models exist. To allow for an improved understanding of these diseases, tissue banks with sufficient amount of samples to cover the extent of diversity of human cancers are required. Additionally, xenograft models that faithfully mimic and span the breadth of human disease are essential to perform meaningful functional experiments. We describe here the establishment of a tissue biobank, patient derived xenografts (PDXs) and cell line models of esophagogastric and pancreatic cancer patients. Biopsy material was grafted into immunocompromised mice and PDXs were used to establish primary cell cultures to perform functional studies. Expression of Hedgehog ligands in patient tumor and matching PDX was assessed by immunohistochemical staining, and quantitative real-time PCR as well as flow cytometry was used for cultured cells. Cocultures with Hedgehog reporter cells were performed to study paracrine signaling potency. Furthermore, SHH expression was modulated in primary cultures using lentiviral mediated knockdown. We have established a panel of 29 PDXs from esophagogastric and pancreatic cancers, and demonstrate that these PDXs mirror several of the (immuno)histological and biochemical characteristics of the original tumors. Derived cell lines can be genetically manipulated and used to further study tumor biology and signaling capacity. In addition, we demonstrate an active (paracrine) Hedgehog signaling mode by both tumor types, the magnitude of which has not been compared directly in previous studies. Our established PDXs and their matching primary cell lines retain important characteristics seen in the original tumors, and this should enable future studies to address the responses of these tumors to different treatment modalities, but also help in gaining mechanistic insight in how some tumors respond to certain regimens and others do not.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 69 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Malaysia 1 1%
Switzerland 1 1%
Unknown 67 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 15 22%
Student > Ph. D. Student 14 20%
Student > Master 12 17%
Student > Bachelor 8 12%
Other 6 9%
Other 4 6%
Unknown 10 14%
Readers by discipline Count As %
Medicine and Dentistry 20 29%
Biochemistry, Genetics and Molecular Biology 15 22%
Agricultural and Biological Sciences 12 17%
Immunology and Microbiology 2 3%
Nursing and Health Professions 1 1%
Other 2 3%
Unknown 17 25%
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 29 March 2016.
All research outputs
#18,449,393
of 22,858,915 outputs
Outputs from Journal of Translational Medicine
#2,950
of 4,001 outputs
Outputs of similar age
#193,294
of 264,662 outputs
Outputs of similar age from Journal of Translational Medicine
#75
of 85 outputs
Altmetric has tracked 22,858,915 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,001 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 17th percentile – i.e., 17% of its peers scored the same or lower than it.
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We're also able to compare this research output to 85 others from the same source and published within six weeks on either side of this one. This one is in the 2nd percentile – i.e., 2% of its contemporaries scored the same or lower than it.