Evidence map›Paper›PMID 25804872›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2015

Targeting of metastasis-promoting tumor-associated fibroblasts and modulation of pancreatic tumor-associated stroma with a carboxymethylcellulose-docetaxel nanoparticle.

Mark J Ernsting, Bryan Hoang, Ines Lohse, Elijus Undzys, Pinjiang Cao, Trevor Do, Bethany Gill, Melania Pintilie, David Hedley, Shyh-Dar Li

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2015. 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
4.9field-weighted citation impact, top 3% 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, 128 citations in OpenAlex.

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  18. Ym1iScience · 2022
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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

10 authors at 4 institutions in 1 country.

Mark J ErnstingDrug Discovery Program, Ontario Institute for Cancer Research, 101 College Street, Suite 800, Toronto, Ontario M5G 0A3, Canada; Faculty of Engineering and Architectural Science, Ryerson University, Toronto, Ontario M5B 1Z2, Canada.
Bryan HoangDrug Discovery Program, Ontario Institute for Cancer Research, 101 College Street, Suite 800, Toronto, Ontario M5G 0A3, Canada.
Ines LohseOntario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2M9, Canada.
Elijus UndzysDrug Discovery Program, Ontario Institute for Cancer Research, 101 College Street, Suite 800, Toronto, Ontario M5G 0A3, Canada.
Pinjiang CaoOntario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2M9, Canada.
Trevor DoSpatio-Temporal Targeting and Amplification of Radiation Response (STTARR) Program, Princess Margaret Hospitals Radiation Medicine Program, Toronto, Ontario M5G 2M9, Canada.
Bethany GillOntario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2M9, Canada.
Melania PintilieOntario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2M9, Canada.
David HedleyOntario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2M9, Canada; Department of Medical Oncology and Haematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Shyh-Dar LiDrug Discovery Program, Ontario Institute for Cancer Research, 101 College Street, Suite 800, Toronto, Ontario M5G 0A3, Canada; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. Electronic address: shyh-dar.li@ubc.ca.
Ontario Institute for Cancer Research · CAUniversity Health Network · CAPrincess Margaret Cancer Centre · CAUniversity of British Columbia · CA

Funding

Stromal depletion for pancreatic cancer therapyR21CA176339 · NCI · UNIVERSITY OF BRITISH COLUMBIA · PI FOLTZ, WARREN, HEDLEY, DAVID · 2013 to 2014
$374k
Canadian Institutes of Health Research MSH-130195Canadian Institutes of Health Research PPP-122898NCI NIH HHS CA17633901NCI NIH HHS R21 CA176339
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinomas are characterized by the desmoplastic reaction, a dense fibrous stroma that has been shown to be supportive of tumor cell growth, invasion, and metastasis, and has been associated with resistance to chemotherapy and reduced patient survival. Here, we investigated targeted depletion of stroma for pancreatic cancer therapy via taxane nanoparticles. Cellax-DTX polymer is a conjugate of docetaxel (DTX), polyethylene glycol (PEG), and acetylated carboxymethylcellulose, a construct which condenses into well-defined 120nm particles in an aqueous solution, and is suitable for intravenous injection. We examined Cellax-DTX treatment effects in highly stromal primary patient-derived pancreatic cancer xenografts and in a metastatic PAN02 mouse model of pancreatic cancer, focusing on specific cellular interactions in the stroma, pancreatic tumor growth and metastasis. Greater than 90% of Cellax-DTX particles accumulate in smooth muscle actin (SMA) positive cancer-associated fibroblasts which results in long-term depletion of this stromal cell population, an effect not observed with Nab-paclitaxel (Nab-PTX). The reduction in stromal density leads to a >10-fold increase in tumor perfusion, reduced tumor weight and a reduction in metastasis. Consentingly, Cellax-DTX treatment increased survival when compared to treatment with gemcitabine or Nab-PTX in a metastatic PAN02 mouse model. Cellax-DTX nanoparticles interact with the tumor-associated stroma, selectively interacting with and depleting SMA positive cells and macrophage, effects of which are associated with significant changes in tumor progression and metastasis.

Indexed as

AnimalsAntineoplastic AgentsCarboxymethylcellulose SodiumCell Line, TumorDocetaxelDrug Delivery SystemsFemaleFibroblastsHumansMiceMice, Inbred C57BLNanoparticlesNeoplasm MetastasisPancreasPancreatic NeoplasmsPolyethylene GlycolsAntineoplastic AgentsCarboxymethylcellulose SodiumDocetaxelPolyethylene GlycolsTaxoidsNanoparticlesPancreatic cancerTumor-associated stroma

Identifiers

PMID25804872
PMCPMC4409566
OpenAlexW2025222792

What OpenQuestion holds

Textmetadata
LicenceTDM
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.