Evidence map›Paper›PMID 24852095›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2014

Improving the distribution of Doxil® in the tumor matrix by depletion of tumor hyaluronan.

Aditya G Kohli, Saul Kivimäe, Matthew R Tiffany, Francis C Szoka

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 9% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Tumor-ColonizingBiomolecules · 2024
    Article
  8. Review
  9. Review
  10. A Magnetically Driven Amoeba-Like Nanorobot for Whole-Process Active Drug Transport.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  11. Review
  12. Review
  13. Article
  14. Extracellular matrix and its therapeutic potential for cancer treatment.Signal transduction and targeted therapy · 2021
    Review
  15. Review
  16. Review
  17. Article
  18. Antifibrotic therapy to normalize the tumor microenvironment.Journal of translational medicine · 2020
    Review
  19. Review
  20. Article
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

4 authors at 2 institutions in 1 country.

Aditya G KohliThe UC-Berkeley-UCSF Graduate Program in Bioengineering, University of California Berkeley, Berkeley 94720, USA; Department of Bioengineering, Therapeutic Sciences and Pharmaceutical Chemistry, University of California San Francisco, San Francisco 94143, USA.
Saul KivimäeDepartment of Bioengineering, Therapeutic Sciences and Pharmaceutical Chemistry, University of California San Francisco, San Francisco 94143, USA.
Matthew R TiffanyDepartment of Bioengineering, Therapeutic Sciences and Pharmaceutical Chemistry, University of California San Francisco, San Francisco 94143, USA; Pharmaceutical Sciences and Pharmacogenomics Graduate Program, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco 94143, USA.
Francis C SzokaThe UC-Berkeley-UCSF Graduate Program in Bioengineering, University of California Berkeley, Berkeley 94720, USA; Department of Bioengineering, Therapeutic Sciences and Pharmaceutical Chemistry, University of California San Francisco, San Francisco 94143, USA; Pharmaceutical Sciences and Pharmacogenomics Graduate Program, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco 94143, USA. Electronic address: szoka@cgl.ucsf.edu.
University of California, San Francisco · USUniversity of California, Berkeley · US

Funding

Targeted Drug Delivery to Surface Receptors.R01GM061851 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SZOKA, FRANCIS C. · 2001 to 2015
$3.5M
NIGMS NIH HHS R01 GM061851NIGMS NIH HHS R01GM061851
6 · The paper itself

Abstract

Liposomes improve the pharmacokinetics and safety of rapidly cleared drugs, but have not yet improved the clinical efficacy compared to the non-encapsulated drug. This inability to improve efficacy may be partially due to the non-uniform distribution of liposomes in solid tumors. The tumor extra-cellular matrix is a barrier to distribution and includes the high molecular weight glycosaminoglycan, hyaluronan (HA). Strategies to remove HA or block its synthesis may improve drug delivery into solid tumors. Orally administered methylumbelliferone (MU) is an inhibitor of HA synthesis, but it is limited by low potency and limited solubility. In this study, we encapsulate a water-soluble phosphorylated prodrug of MU (MU-P) in a liposome (L-MU-P). We demonstrate that L-MU-P is a more potent inhibitor of HA synthesis than oral MU in the 4T1 murine mammary carcinoma model using both a quantitative ELISA and histochemistry. We show that HA depletion improves the tumor distribution of liposomes computed using Mander's colocalization analysis of liposomes with the tumor vasculature. Hyaluronan depletion also increases the fraction of the tumor area positive for liposomes. This improved distribution extends the overall survival of mice treated with Doxil®.

Indexed as

Administration, OralAnimalsAntibiotics, AntineoplasticCell Line, TumorDoxorubicinFemaleHyaluronic AcidHymecromoneInjections, IntravenousMammary Neoplasms, ExperimentalMice, Inbred BALB CPhosphorylationPolyethylene GlycolsProdrugsSolubilityTime FactorsAntibiotics, AntineoplasticDoxorubicinHyaluronic AcidHymecromoneliposomal doxorubicinPolyethylene GlycolsProdrugsBreast cancerExtra-cellular matrixLiposomesTumor penetration

Identifiers

PMID24852095
PMCPMC4156903
OpenAlexW2093429871

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.