Evidence map›Paper›PMID 32253045›Full record

ArticleGynecologic oncology2020

Short-term organoid culture for drug sensitivity testing of high-grade serous carcinoma.

Hui Chen, Kristin Gotimer, Cristabelle De Souza, Clifford G Tepper, Anthony N Karnezis, Gary S Leiserowitz, Jeremy Chien, Lloyd H Smith

Open access · bronzeAbstract read
In one paragraph

Article in Gynecologic oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 5% 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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.

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  20. Addressing Key Questions in Organoid Models: Who, Where, How, and Why?International journal of molecular sciences · 2023
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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

8 authors at 1 institution in 1 country.

Hui ChenDepartment of Obstetrics and Gynecology, University of California Davis Health, Sacramento, CA 95817, United States of America.
Kristin GotimerDepartment of Obstetrics and Gynecology, University of California Davis Health, Sacramento, CA 95817, United States of America.
Cristabelle De SouzaDepartment of Biochemistry and Molecular Medicine, University of California Davis Health, Sacramento, CA 95817, United States of America.
Clifford G TepperDepartment of Biochemistry and Molecular Medicine, University of California Davis Health, Sacramento, CA 95817, United States of America.
Anthony N KarnezisDepartment of Pathology and Laboratory Medicine, University of California Davis Health, Sacramento, CA 95817, United States of America.
Gary S LeiserowitzDepartment of Obstetrics and Gynecology, University of California Davis Health, Sacramento, CA 95817, United States of America.
Jeremy ChienDepartment of Obstetrics and Gynecology, University of California Davis Health, Sacramento, CA 95817, United States of America; Department of Biochemistry and Molecular Medicine, University of California Davis Health, Sacramento, CA 95817, United States of America. Electronic address: jrchien@ucdavis.edu.
Lloyd H SmithDepartment of Obstetrics and Gynecology, University of California Davis Health, Sacramento, CA 95817, United States of America. Electronic address: lhsmith@ucdavis.edu.
University of California, Davis · US

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Laura Marcu · 2002 to 2026
$84.9M
NCI NIH HHS P30 CA093373
6 · The paper itself

Abstract

objectiveCancer patient-derived organoids (PDOs) grow as three dimensional (3D) structures in the presence of extracellular matrix and have been found to represent the original tumor's genetic complexity. In addition, PDOs can be grown and subjected to drug sensitivity testing in a shorter time course and with lesser expense than patient-derived xenograft models. Many patients with recurrent ovarian cancer develop malignant effusions that become refractory to chemotherapy. Since these same patients often present for palliative aspiration of ascites or pleural effusions, there is a potential opportunity to obtain tumor specimens in the form of multicellular spheroids (MCS) present in malignant effusion fluids. Our objective was to develop a short duration culture of MCS from ovarian cancer malignant effusions in conditions selected to support organoid growth and use them as a platform for empirical drug sensitivity testing.

methodsIn this study, malignant effusion specimens were collected from patients with high-grade serous ovarian carcinoma (HGSOC). MCS were recovered and subjected to culture conditions designed to support organoid growth. In a subset of specimens, RNA-sequencing was performed at two time points during the short-term culture to determine changes in transcriptome in response to culture conditions. Organoid induction was also characterized in these specimens using Ki67 staining and histologic analysis. Drug sensitivity testing was performed on all specimens.

resultsOur model describes organoids formed within days of primary culture, which can recapitulate the histological features of malignant ascites fluid and can be expanded for at least 6 days. RNA-seq analysis of four patient specimens showed that within 6 days of culture, there was significant up-regulation of genes related to cellular proliferation, epithelial-mesenchymal transition, and KRAS signaling pathways. Drug sensitivity testing identified several agents with therapeutic potential.

conclusionsShort duration organoid culture of MCS from HGSOC malignant effusions can be used as a platform for empiric drug sensitivity testing. These ex vivo models may be helpful in screening new or existing therapeutic agents prior to individualized treatment options.

Indexed as

AgedCystadenoma, SerousFemaleHumansMiddle AgedNeoplasm GradingOrgan Culture TechniquesOrganoidsOvarian NeoplasmsMulticellular spheroidsOvarian cancerPatient-derived organoid modelsTargeted experimental therapeutics

Identifiers

PMID32253045
PMCPMC7819712
OpenAlexW3014215983

What OpenQuestion holds

Textmetadata
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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.