ArticlePloS one2011
Conditionally replicating adenovirus expressing TIMP2 increases survival in a mouse model of disseminated ovarian cancer.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Non-pharmacological interventions for vascular health and the role of the endothelium.European journal of applied physiology · 2022Review
- Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents.Journal of ovarian research · 2019Article
- Dysregulation of fibulin-5 and matrix metalloproteases in epithelial ovarian cancer.Oncotarget · 2018Article
- The Many Facets of Metzincins and Their Endogenous Inhibitors: Perspectives on Ovarian Cancer Progression.International journal of molecular sciences · 2018Review
- Establishment of a novel method to evaluate peritoneal microdissemination and therapeutic effect using luciferase assay.Cancer science · 2016Article
- Tissue inhibitor of metalloproteinase 2 inhibits activation of the β-catenin signaling in melanoma cells.Cell cycle (Georgetown, Tex.) · 2015Article
- SPARCL1 suppresses metastasis in prostate cancer.Molecular oncology · 2013Article
- Hypoxia- and radiation-induced overexpression of Smac by an adenoviral vector and its effects on cell cycle and apoptosis in MDA-MB-231 human breast cancer cells.Experimental and therapeutic medicine · 2013Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Ovarian cancer remains difficult to treat mainly due to presentation of the disease at an advanced stage. Conditionally-replicating adenoviruses (CRAds) are promising anti-cancer agents that selectively kill the tumor cells. The present study evaluated the efficacy of a novel CRAd (Ad5/3-CXCR4-TIMP2) containing the CXCR4 promoter for selective viral replication in cancer cells together with TIMP2 as a therapeutic transgene, targeting the matrix metalloproteases (MMPs) in a murine orthotopic model of disseminated ovarian cancer. An orthotopic model of ovarian cancer was established in athymic nude mice by intraperitonal injection of the human ovarian cancer cell line, SKOV3-Luc, expressing luciferase. Upon confirmation of peritoneal dissemination of the cells by non-invasive imaging, mice were randomly divided into four treatment groups: PBS, Ad-ΔE1-TIMP2, Ad5/3-CXCR4, and Ad5/3-CXCR4-TIMP2. All mice were imaged weekly to monitor tumor growth and were sacrificed upon reaching any of the predefined endpoints, including high tumor burden and significant weight loss along with clinical evidence of pain and distress. Survival analysis was performed using the Log-rank test. The median survival for the PBS cohort was 33 days; for Ad-ΔE1-TIMP2, 39 days; for Ad5/3-CXCR4, 52.5 days; and for Ad5/3-CXCR4-TIMP2, 63 days. The TIMP2-armed CRAd delayed tumor growth and significantly increased survival when compared to the unarmed CRAd. This therapeutic effect was confirmed to be mediated through inhibition of MMP9. Results of the in vivo study support the translational potential of Ad5/3-CXCR4-TIMP2 for treatment of human patients with advanced ovarian cancer.
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