Evidence map›Paper›PMID 14605668›Full record

ArticleCancer gene therapy2003

A novel antisense inhibitor of MMP-9 attenuates angiogenesis, human prostate cancer cell invasion and tumorigenicity.

Carla A London, Harmanjatinder S Sekhon, Vikram Arora, David A Stein, Patrick L Iversen, Gayathri R Devi

Abstract read
PubMed Publisher
In one paragraph

Article in Cancer gene therapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Andrographolide Enhances TRAIL-Induced Apoptosis viaInternational journal of biological sciences · 2019
    Article
  9. Nanoparticle-mediated siRNA Gene-silencing in Adult Zebrafish Heart.Journal of visualized experiments : JoVE · 2018
    Article
  10. Article
  11. Prognostic significance of the tumour-adjacent tissue in head and neck cancers.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. In vivo electroporation of morpholinos into the adult zebrafish retina.Journal of visualized experiments : JoVE · 2011
    Article
  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

6 authors at 2 institutions in 1 country.

Carla A LondonAVI BioPharma Inc., 4575 SW Research Way, Suite 200, Corvallis, Oregon 97333, USA.
Harmanjatinder S Sekhon
Vikram Arora
David A Stein
Patrick L Iversen
Gayathri R Devi
Sarepta Therapeutics (United States) · USOregon Health & Science University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Androgen deprivation therapy causes a paradoxical elevation of matrix metalloproteinases (MMPs) including MMP-9 resulting in aggressive tumor phenotype in many patients with prostate cancer. In this study, we have evaluated a novel antisense phosphorodiamidate Morpholino oligomer (PMO) targeted against MMP-9 in models of angiogenesis and in human prostate xenograft in athymic mice. The treatment of androgen-independent DU145 human prostate cells with a 21-mer MMP-9 antisense PMO caused a dose-dependent inhibition of cell proliferation compared to scrambled or MMP-2 antisense PMO at similar concentrations. This was associated with decreases in MMP-9 expression, gelatinolytic activity and increased stability of the insulin-like growth factor-binding protein (IGFBP-3), a proapoptotic factor and MMP-9 substrate. In vitro invasion assays revealed a 40-60% inhibition of DU145 cell invasion in the presence of 25 microM MMP-9 antisense PMO. A significant decrease in endothelial cell migration and vascularization was observed in the Matrigel plug assay in mice when treated intraperitoneally with 300 microg/day MMP-9 antisense for 21 days. In the highly vascular DU145 tumor xenografts, MMP-9 inhibition caused decreased tumor growth with regression in 50% of the animals. Histological analysis revealed increased apoptosis and fibrous tissue deposits in the MMP-9 antisense-treated tumors compared to the scrambled and saline controls. No apparent toxicity or mortality was associated with the MMP-9 PMO treatment. In summary, the MMP-9 antisense PMO inhibited in vitro prostate cancer cell proliferation, invasion and in vivo angiogenesis. These data establish the feasibility of developing a site-directed, nontoxic antisense therapeutic agent for inhibiting local invasion and metastasis.

Indexed as

Matrix Metalloproteinase InhibitorsAngiogenesis InhibitorsAnimalsCarcinogenicity TestsCell SurvivalEnzyme InhibitorsHumansInsulin-Like Growth Factor Binding Protein 3MaleMatrix Metalloproteinase 9MiceMice, NudeNeoplasm InvasivenessNeovascularization, PathologicOligonucleotides, AntisenseProstateAngiogenesis InhibitorsEnzyme InhibitorsInsulin-Like Growth Factor Binding Protein 3Matrix Metalloproteinase 9Matrix Metalloproteinase InhibitorsOligonucleotides, Antisense

Identifiers

PMID14605668
OpenAlexW2078241670

What OpenQuestion holds

Textmetadata
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.