Evidence map›Paper›PMID 14681728›Full record

ArticleCancer gene therapy2004

AAV-mediated gene transfer of tissue inhibitor of metalloproteinases-1 inhibits vascular tumor growth and angiogenesis in vivo.

Serena Zacchigna, Lorena Zentilin, Monica Morini, Raffaella Dell'Eva, Douglas M Noonan, Adriana Albini, Mauro Giacca

Abstract read
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In one paragraph

Article in Cancer gene therapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.3field-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

22 citing papers in PubMed, 58 citations in OpenAlex.

  1. Review
  2. The RNA-Binding Proteins MCPIP2 and IGF2BP1 Competitively Modulate Breast Tumor Angiogenesis by Antagonizing VEGFA mRNA Stability and Expression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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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

7 authors at 2 institutions in 1 country.

Serena ZacchignaMolecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Lorena Zentilin
Monica Morini
Raffaella Dell'Eva
Douglas M Noonan
Adriana Albini
Mauro Giacca
Alleanza Contro il Cancro · ITInternational Centre for Genetic Engineering and Biotechnology · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The activity of matrix metalloproteinases (MMPs) is a universal feature of cellular invasion, tumor angiogenesis and metastasis, which is counterbalanced and regulated by the natural tissue inhibitors of MMPs (Timps). Here we show that Timp1 gene transfer delivered by an adeno-associated virus (AAV) vector inhibits tumor growth in a murine xenotransplant model. A human Kaposi's sarcoma cell line, forming highly vascularized tumors in vivo and having a high natural permissivity to AAV gene transfer, was transduced to express the Timp1 cDNA. AAV-Timp1-transduced cells secreted high levels of Timp1 that inhibited MMP2 and MMP9 gelatinolytic activity. Following subcutaneous inoculation in nude mice, the AAV-Timp1-transduced cells showed significantly reduced tumor growth when compared to control AAV-LacZ-transduced cells. In addition, direct intratumoral injection of AAV-Timp1 into pre-existing tumors significantly impaired the further expansion of the tumor mass. Histological analyses showed that the AAV-Timp1-transduced tumors had limited development of vascular structures and extensive areas of cell death, suggesting that Timp1 overexpression had an antiangiogenic effect. To further support this conclusion, we demonstrated that AAV-Timp1 transduction significantly reduced endothelial cell migration and the invasion of a Matrigel barrier and strongly inhibited angiogenesis in the chick chorioallantoic membrane assay. These results indicate that transfer and overexpression of the Timp1 gene is a promising therapeutic strategy to target tumor-associated angiogenesis in cancer gene therapy.

Indexed as

Genetic TherapyAnimalsBasement MembraneCell DivisionCell Line, TumorCell MovementDependovirusEndothelial CellsGene Transfer TechniquesHumansMiceNeoplasm InvasivenessNeoplasm TransplantationNeovascularization, PathologicSarcoma, KaposiTissue Inhibitor of Metalloproteinase-1Tissue Inhibitor of Metalloproteinase-1

Identifiers

PMID14681728
OpenAlexW2018271388

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.