Evidence map›Paper›PMID 29054369›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2017

Exosome is a mechanism of intercellular drug transfer: Application of quantitative pharmacology.

Jin Wang, Bertrand Z Yeung, Minjian Cui, Cody J Peer, Ze Lu, William D Figg, M Guillaume Wientjes, Sukyung Woo, Jessie L-S Au

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

42 citing papers in PubMed, 83 citations in OpenAlex.

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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

9 authors at 4 institutions in 2 countries.

Jin WangDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA; Institute of Quantitative Systems Pharmacology, Carlsbad, CA 92008, USA.
Bertrand Z YeungDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA; Institute of Quantitative Systems Pharmacology, Carlsbad, CA 92008, USA; Optimum Therapeutics LLC, Carlsbad, CA 92008, USA.
Minjian CuiDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA; Institute of Quantitative Systems Pharmacology, Carlsbad, CA 92008, USA; Optimum Therapeutics LLC, Carlsbad, CA 92008, USA.
Cody J PeerClinical Pharmacology Program, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Ze LuOptimum Therapeutics LLC, Carlsbad, CA 92008, USA.
William D FiggClinical Pharmacology Program, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
M Guillaume WientjesInstitute of Quantitative Systems Pharmacology, Carlsbad, CA 92008, USA; Optimum Therapeutics LLC, Carlsbad, CA 92008, USA.
Sukyung WooDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.
Jessie L-S AuDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA; Institute of Quantitative Systems Pharmacology, Carlsbad, CA 92008, USA; Optimum Therapeutics LLC, Carlsbad, CA 92008, USA; College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: jau@optimumtx.com.
Quantitative BioSciences · USNational Cancer Institute · USOptimum Therapeutics (United States) · USUniversity of Oklahoma Health Sciences Center · US

Funding

Using Clinical Pharmacology Principles to Develop New Anticancer TherapiesZICSC006537 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI FIGG, WILLIAM DOUGLAS · 2009 to 2025
$14.4M
Targeting multiple signaling steps to achieve synergyR01CA163015 · NCI · OPTIMUM THERAPEUTICS, LLC · PI AU, JESSIE L.-S., WIENTJES, M GUILLAUME · 2012 to 2017
$1.9M
Synergistic chemo-siRNA combination therapyR01CA158300 · NCI · OPTIMUM THERAPEUTICS, LLC · PI AU, JESSIE L.-S., WIENTJES, M GUILLAUME · 2011 to 2015
$1.8M
Multiscale computational models for developing combination cancer therapyR01GM100487 · NIGMS · OPTIMUM THERAPEUTICS, LLC · PI AU, JESSIE L.-S., WIENTJES, M GUILLAUME · 2011 to 2014
$1.3M
Capturing dynamic and inter-dependent biointerfaces in nanotechnology designsR01EB015253 · NIBIB · OPTIMUM THERAPEUTICS, LLC · PI AU, JESSIE L.-S., WIENTJES, M GUILLAUME · 2011 to 2014
$1.1M
NCI NIH HHS R01 CA158300NCI NIH HHS R01 CA163015NIBIB NIH HHS R01 EB015253NIGMS NIH HHS R01 GM100487
6 · The paper itself

Abstract

purposeExosomes are small membrane vesicles (30-100nm in diameter) secreted by cells into extracellular space. The present study evaluated the effect of chemotherapeutic agents on exosome production and/or release, and quantified the contribution of exosomes to intercellular drug transfer and pharmacodynamics.

methodsHuman cancer cells (breast MCF7, breast-to-lung metastatic LM2, ovarian A2780 and OVCAR4) were treated with paclitaxel (PTX, 2-1000nM) or doxorubicin (DOX, 20-1000nM) for 24-48h. Exosomes were isolated from the culture medium of drug-treated donor cells (Donor cells) using ultra-centrifugation, and analyzed for acetylcholinesterase activity, total proteins, drug concentrations, and biological effects (cytotoxicity and anti-migration) on drug-naïve recipient cells (Recipient cells). These results were used to develop computational predictive quantitative pharmacology models.

resultsCells in exponential growth phase released ~220 exosomes/cell in culture medium. PTX and DOX significantly promoted exosome production and/or release in a dose- and time-dependent manner, with greater effects in ovarian cancer cells than in breast cancer cells. Exosomes isolated from Donor cells contained appreciable drug levels (2-7pmole/10

conclusionsOur results indicate (a) chemotherapeutic agents stimulate exosome production or release, and (b) exosome is a mechanism of intercellular drug transfer that contributes to pharmacodynamics of neighboring cells.

Indexed as

Models, BiologicalAntineoplastic AgentsBiological TransportCell Line, TumorCell SurvivalDoxorubicinExosomesHumansPaclitaxelPharmacologyAntineoplastic AgentsDoxorubicinPaclitaxelChemoresistanceExocytosisExosomeIntercellular drug transferQuantitative pharmacology

Identifiers

PMID29054369
PMCPMC5722714
OpenAlexW2766012762

What OpenQuestion holds

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Registered trials

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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.