Evidence map›Paper›PMID 29747161›Full record

ArticleNeoplasia (New York, N.Y.)2018

A 3D Human Renal Cell Carcinoma-on-a-Chip for the Study of Tumor Angiogenesis.

Chris P Miller, Connor Tsuchida, Ying Zheng, Jonathan Himmelfarb, Shreeram Akilesh

Open access · goldAbstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 104 citations in OpenAlex.

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  16. Microphysiological systems as models for immunologically 'cold' tumors.Frontiers in cell and developmental biology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Chris P MillerDepartment of Medicine/Nephrology, University of Washington, 1959 NE Pacific Street, Box 356521, Health Sciences Building, BB-1271, Seattle, WA 98195; Kidney Research Institute, University of Washington, Box 359606, 325 Ninth Avenue, Seattle, WA 98104; Fred Hutchinson Cancer Research Center / University of Washington Cancer Consortium, 1100 Fairview Ave N, Seattle, WA 98109. Electronic address: cpmiller@uw.edu.
Connor TsuchidaDepartment of Bioengineering, University of Washington, Box 355061, William H. Foege Building, 3720 15th Ave NE, Seattle, WA 98195. Electronic address: ctsuchida51@yahoo.com.
Ying ZhengKidney Research Institute, University of Washington, Box 359606, 325 Ninth Avenue, Seattle, WA 98104; Fred Hutchinson Cancer Research Center / University of Washington Cancer Consortium, 1100 Fairview Ave N, Seattle, WA 98109; Department of Bioengineering, University of Washington, Box 355061, William H. Foege Building, 3720 15th Ave NE, Seattle, WA 98195; Institute for Stem Cell and Regenerative Medicine, University of Washington, Box 358056, 850 Republican Street Seattle, WA 98109. Electronic address: yingzy@uw.edu.
Jonathan HimmelfarbDepartment of Medicine/Nephrology, University of Washington, 1959 NE Pacific Street, Box 356521, Health Sciences Building, BB-1271, Seattle, WA 98195; Kidney Research Institute, University of Washington, Box 359606, 325 Ninth Avenue, Seattle, WA 98104. Electronic address: Jhimmelfarb@Nephrology.washington.edu.
Shreeram AkileshKidney Research Institute, University of Washington, Box 359606, 325 Ninth Avenue, Seattle, WA 98104; Fred Hutchinson Cancer Research Center / University of Washington Cancer Consortium, 1100 Fairview Ave N, Seattle, WA 98109; Department of Pathology, University of Washington, Box 356100, 1959 NE Pacific Street, Seattle, WA 98195. Electronic address: shreeram@uw.edu.
University of Washington · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
Using iPSCs to model patient outcomes in nephrotic syndromeUH3TR000504 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2014 to 2016
$6.1M
A Tissue Engineered Human Kidney Microphysiological SystemUH2TR000504 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2012 to 2013
$2.1M
NCATS NIH HHS UH2 TR000504NCATS NIH HHS UH3 TR000504NCI NIH HHS P30 CA015704
6 · The paper itself

Abstract

Tractable human tissue-engineered 3D models of cancer that enable fine control of tumor growth, metabolism, and reciprocal interactions between different cell types in the tumor microenvironment promise to accelerate cancer research and pharmacologic testing. Progress to date mostly reflects the use of immortalized cancer cell lines, and progression to primary patient-derived tumor cells is needed to realize the full potential of these platforms. For the first time, we report endothelial sprouting induced by primary patient tumor cells in a 3D microfluidic system. Specifically, we have combined primary human clear cell renal cell carcinoma (ccRCC) cells from six independent donors with human endothelial cells in a vascularized, flow-directed, 3D culture system ("ccRCC-on-a-chip"). The upregulation of key angiogenic factors in primary human ccRCC cells, which exhibited unique patterns of donor variation, was further enhanced when they were cultured in 3D clusters. When embedded in the matrix surrounding engineered human vessels, these ccRCC tumor clusters drove potent endothelial cell sprouting under continuous flow, thus recapitulating the critical angiogenic signaling axis between human ccRCC cells and endothelial cells. Importantly, this phenotype was driven by a primary tumor cell-derived biochemical gradient of angiogenic growth factor accumulation that was subject to pharmacological blockade. Our novel 3D system represents a vascularized tumor model that is easy to image and quantify and is fully tunable in terms of input cells, perfusate, and matrices. We envision that this ccRCC-on-a-chip will be valuable for mechanistic studies, for studying tumor-vascular cell interactions, and for developing novel and personalized antitumor therapies.

Indexed as

Angiogenesis Inducing AgentsCarcinoma, Renal CellCell Culture TechniquesCell Line, TumorEndothelial CellsHumansHuman Umbilical Vein Endothelial CellsKidney NeoplasmsNeovascularization, PathologicAngiogenesis Inducing Agents

Identifiers

PMID29747161
PMCPMC5994779
OpenAlexW2801853197

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.