ArticleNeoplasia (New York, N.Y.)2010
Impact of metronomic UFT/cyclophosphamide chemotherapy and antiangiogenic drug assessed in a new preclinical model of locally advanced orthotopic hepatocellular carcinoma.
Article in Neoplasia (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
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.
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Who cites it
25 citing papers in PubMed.
- Transarterial chemoembolization plus sorafenib: a sequential therapeutic scheme for HCV-related intermediate-stage hepatocellular carcinoma: a randomized clinical trial.The oncologist · 2012Trial
- Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models.Oncotarget · 2020Article
- Fuzheng Qingjie granules potentiate the anticancer effect of cyclophosphamide by regulating cellular immune function and inducing apoptosis in Hepatoma 22 tumor-bearing mice.Oncology letters · 2017Article
- IGF2 Is Up-regulated by Epigenetic Mechanisms in Hepatocellular Carcinomas and Is an Actionable Oncogene Product in Experimental Models.Gastroenterology · 2016Article
- Co-option of Liver Vessels and Not Sprouting Angiogenesis Drives Acquired Sorafenib Resistance in Hepatocellular Carcinoma.Journal of the National Cancer Institute · 2016Article
- Effects of Sorafenib Dose on Acquired Reversible Resistance and Toxicity in Hepatocellular Carcinoma.Cancer research · 2015Article
- Hesperetin induces the apoptosis of hepatocellular carcinoma cells via mitochondrial pathway mediated by the increased intracellular reactive oxygen species, ATP and calcium.Medical oncology (Northwood, London, England) · 2015Article
- Combinations of vascular endothelial growth factor pathway inhibitors with metronomic chemotherapy: Rational and current status.World journal of experimental medicine · 2014Review
- SNS01-T modulation of eIF5A inhibits B-cell cancer progression and synergizes with bortezomib and lenalidomide.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells.Cell death & disease · 2014Article
- Wentilactone B induces G2/M phase arrest and apoptosis via the Ras/Raf/MAPK signaling pathway in human hepatoma SMMC-7721 cells.Cell death & disease · 2013Article
- Metronomic chemotherapy: possible clinical application in advanced hepatocellular carcinoma.Translational oncology · 2013Review
- Overcoming intratumor heterogeneity of polygenic cancer drug resistance with improved biomarker integration.Neoplasia (New York, N.Y.) · 2012Article
- Metronomic chemotherapy in combination with antiangiogenic treatment induces mosaic vascular reduction and tumor growth inhibition in hepatocellular carcinoma xenografts.Journal of cancer research and clinical oncology · 2012Article
- Article
- Improved intratumoral delivery of PEG-coated siRNA-lipoplexes by combination with metronomic S-1 dosing in a murine solid tumor model.Drug delivery and translational research · 2012Article
- The interconnectedness of cancer cell signaling.Neoplasia (New York, N.Y.) · 2011Article
- Hepatocellular carcinoma: insight from animal models.Nature reviews. Gastroenterology & hepatology · 2011Review
- Metronomic oral topotecan with pazopanib is an active antiangiogenic regimen in mouse models of aggressive pediatric solid tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2011Article
- Metronomic S-1 chemotherapy and vandetanib: an efficacious and nontoxic treatment for hepatocellular carcinoma.Neoplasia (New York, N.Y.) · 2011Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Hepatocellular carcinoma (HCC) is an intrinsically chemotherapy refractory malignancy. Development of effective therapeutic regimens would be facilitated by improved preclinical HCC models. Currently, most models consist of subcutaneous human tumor transplants in immunodeficient mice; however, these do not reproduce the extensive liver disease associated with HCC or metastasize. To address this deficiency, we developed an orthotopic model. Human HCC cells were transfected with the gene encoding secretable beta-subunit human choriogonadotropin (beta-hCG), which was used as a surrogate marker of tumor burden. The HCC cells were implanted into the left liver lobe of severe combined immunodeficient (SCID) mice, after which the efficacy of different therapies was evaluated on established, but liver-confined human Hep3B cell line HCC. Treatments included sorafenib or metronomic chemotherapy using cyclophosphamide (CTX), UFT, an oral 5-fluorouracil prodrug, or doxorubicin either alone or in various combinations, with or without an antiangiogenic agent, DC101, an anti-vascular endothelial growth factor receptor-2 antibody. Sorafenib inhibited tumor growth in a dose-dependent manner but caused severe weight loss in SCID mice, thus necessitating use of DC101 in subsequent experiments. Although less toxicity was observed using either single or doublet metronomic chemotherapy without any added antiangiogenic agent, none, provided survival benefit. In contrast, significantly improved overall survival was observed using various combinations of metronomic chemotherapy regimens such as UFT + CTX with DC101. In conclusion, using this model of liver-confined but advanced HCC suggests that the efficacy of a targeted antiangiogenic drug or metronomic chemotherapy can be mutually enhanced by concurrent combination treatment.
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Registered trials
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.