ArticleCancer science2009
Systemic NK4 gene therapy inhibits tumor growth and metastasis of melanoma and lung carcinoma in syngeneic mouse tumor models.
Article in Cancer science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Beyond cancer cells: Targeting the tumor microenvironment with gene therapy and armed oncolytic virus.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Tumor angiogenesis and anti-angiogenic gene therapy for cancer.Oncology letters · 2018Review
- YangZheng XiaoJi exerts anti-tumour growth effects by antagonising the effects of HGF and its receptor, cMET, in human lung cancer cells.Journal of translational medicine · 2015Article
- Article
- Regulation of hepatocyte growth factor in mice with pneumonia by peptidases and trans-alveolar flux.PloS one · 2015Article
- A clinical protocol to inhibit the HGF/c-Met pathway for malignant mesothelioma with an intrapleural injection of adenoviruses expressing the NK4 gene.SpringerPlus · 2015Article
- [Dysregulation of HGF/c-Met signal pathway and their targeting drugs in lung cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2014Review
- Features and prognostic impact of distant metastasis in patients with stage IV lung adenocarcinoma harboring EGFR mutations: importance of bone metastasis.Clinical & experimental metastasis · 2014Article
- Osteolytic bone metastasis is hampered by impinging on the interplay among autophagy, anoikis and ossification.Cell death & disease · 2014Article
- Mesenchymal stem cell-based NK4 gene therapy in nude mice bearing gastric cancer xenografts.Drug design, development and therapy · 2014Article
- HGF-MET cascade, a key target for inhibiting cancer metastasis: the impact of NK4 discovery on cancer biology and therapeutics.International journal of molecular sciences · 2013Article
- Targeting the HGF-cMET Axis in Hepatocellular Carcinoma.International journal of hepatology · 2013Article
- Targeting the HGF/Met signaling pathway in cancer therapy.Expert opinion on therapeutic targets · 2012Review
- Scavenger receptors and their potential as therapeutic targets in the treatment of cardiovascular disease.International journal of hypertension · 2010Article
- Organ-specific shifts in mtDNA heteroplasmy following systemic delivery of a mitochondria-targeted restriction endonuclease.Gene therapy · 2010Article
- Does hepatocyte growth factor/c-Met signal play synergetic role in lung cancer?Journal of cellular and molecular medicine · 2010Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte growth factor (HGF) promotes malignant development of cancer cells by enhancing invasion and metastasis. NK4, a competitive antagonist for HGF, is a bifunctional molecule that acts as a HGF antagonist and angiogenesis inhibitor. Although successful tumor inhibition by NK4 gene expression in tumor models has been demonstrated, the effects of systemic NK4 gene introduction are yet to be addressed. Here we show that systemic administration of a replication-defective adenovirus expressing NK4 (Ad.NK4) inhibits tumor growth and lung metastasis of B16F10 melanoma and Lewis lung carcinoma in syngeneic mice. Single tail-vein injection of Ad.NK4 achieved therapeutic levels of NK4 in the circulation and in multiple organs. Despite NK4 expression that was highest in the liver, toxicity in the liver was minimal. Ad.NK4-mediated growth inhibition was associated with decreased blood vessel density and increased apoptosis in tumor tissues, which suggests that NK4 suppressed tumor growth as an angiogenesis inhibitor. Metastasis of B16F10 melanoma and Lewis lung carcinoma cells to the lung was potently inhibited by systemic Ad.NK4-administration. Our results demonstrated that the adenovirus-mediated induction of high levels of circulating NK4 significantly inhibited in vivo tumor growth and distant metastasis without obvious side effects. NK4 gene therapy is thus a safe and promising strategy for the treatment of cancer patients, and further validation in clinical trials is needed.
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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.