Evidence map›Paper›PMID 31299607›Full record

ArticleNeoplasia (New York, N.Y.)2019

Engineered 3D Model of Cancer Stem Cell Enrichment and Chemoresistance.

Maria R Ward Rashidi, Pooja Mehta, Michael Bregenzer, Shreya Raghavan, Elyse M Fleck, Eric N Horst, Zainab Harissa, Visweswaran Ravikumar, Samuel Brady, Andrea Bild and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neoplasia (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 2 pooled it
3.3field-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

45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.

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  19. Quiescent Ovarian Cancer Cells Secrete Follistatin to Induce Chemotherapy Resistance in Surrounding Cells in Response to Chemotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
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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

13 authors at 5 institutions in 1 country.

Maria R Ward RashidiDepartment of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, USA.
Pooja MehtaDepartment of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, USA.
Michael BregenzerDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Shreya RaghavanDepartment of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, USA.
Elyse M FleckDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Eric N HorstDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Zainab HarissaDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Visweswaran RavikumarDepartment of Bioinformatics and Computational Biology, Division of Quantitative Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Samuel BradyDepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
Andrea BildDivision of Molecular Pharmacology, Department of Medical Oncology and Therapeutics, City of Hope Cancer Institute, Duarte, CA, USA.
Arvind RaoDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Radiation Oncology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Ronald J BuckanovichDirector of Ovarian Cancer Research, Magee Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Geeta MehtaDepartment of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI, USA.. Electronic address: mehtagee@umich.edu.
University of Michigan–Ann Arbor · USCity of Hope · USThe University of Texas MD Anderson Cancer Center · USUniversity of Pittsburgh · USUniversity of Utah · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
Tissue Engineering and RegenerationT32DE007057 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID H. KOHN · 1985 to 2026
$17.3M
Project 2: Targeting Cooperative Phenotypes Common in Spatial HeterogeneityU54CA209978 · NCI · UNIVERSITY OF UTAH · PI BILD, ANDREA HOPE · 2017 to 2021
$10.5M
NCI NIH HHS P30 CA046592NCI NIH HHS U54 CA209978NIDCR NIH HHS T32 DE007057
6 · The paper itself

Abstract

Intraperitoneal dissemination of ovarian cancers is preceded by the development of chemoresistant tumors with malignant ascites. Despite the high levels of chemoresistance and relapse observed in ovarian cancers, there are no in vitro models to understand the development of chemoresistance in situ.

methodWe describe a highly integrated approach to establish an in vitro model of chemoresistance and stemness in ovarian cancer, using the 3D hanging drop spheroid platform. The model was established by serially passaging non-adherent spheroids. At each passage, the effectiveness of the model was evaluated via measures of proliferation, response to treatment with cisplatin and a novel ALDH1A inhibitor. Concomitantly, the expression and tumor initiating capacity of cancer stem-like cells (CSCs) was analyzed. RNA-seq was used to establish gene signatures associated with the evolution of tumorigenicity, and chemoresistance. Lastly, a mathematical model was developed to predict the emergence of CSCs during serial passaging of ovarian cancer spheroids.

resultsOur serial passage model demonstrated increased cellular proliferation, enriched CSCs, and emergence of a platinum resistant phenotype. In vivo tumor xenograft assays indicated that later passage spheroids were significantly more tumorigenic with higher CSCs, compared to early passage spheroids. RNA-seq revealed several gene signatures supporting the emergence of CSCs, chemoresistance, and malignant phenotypes, with links to poor clinical prognosis. Our mathematical model predicted the emergence of CSC populations within serially passaged spheroids, concurring with experimentally observed data.

conclusionOur integrated approach illustrates the utility of the serial passage spheroid model for examining the emergence and development of chemoresistance in ovarian cancer in a controllable and reproducible format.

Indexed as

AnimalsAntineoplastic AgentsBiomarkersCell Culture TechniquesCell Line, TumorCell ProliferationCell SurvivalCisplatinComputational BiologyDisease Models, AnimalDose-Response Relationship, DrugDrug Resistance, NeoplasmFemaleFlow CytometryGene Expression ProfilingHumansAntineoplastic AgentsBiomarkersCisplatin

Identifiers

PMID31299607
PMCPMC6624324
OpenAlexW2962619065

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.