ArticleAngiogenesis2016
The differential effects of metronomic gemcitabine and antiangiogenic treatment in patient-derived xenografts of pancreatic cancer: treatment effects on metabolism, vascular function, cell proliferation, and tumor growth.
Article in Angiogenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Metabolic Response to an Individualized Multimodal Treatment Strategy in Advanced Pancreatic Adenocarcinoma: A Case Report.Current oncology (Toronto, Ont.) · 2026Article
- Metabolic reprogramming and functional crosstalk within the tumor microenvironment (TME) and A Multi-omics anticancer approach.Medical oncology (Northwood, London, England) · 2025Review
- Tumor Organoids Grown in Mixed-Composition Hydrogels Recapitulate the Plasticity of Pancreatic Cancers.Gels (Basel, Switzerland) · 2025Article
- Computational simulations of tumor growth and treatment response: Benefits of high-frequency, low-dose drug regimens and concurrent vascular normalization.PLoS computational biology · 2023Article
- Functional biomarkers derived from computed tomography and magnetic resonance imaging differentiate PDAC subgroups and reveal gemcitabine-induced hypo-vascularization.European journal of nuclear medicine and molecular imaging · 2022Article
- Translational Learnings in the Development of Chemo-Immunotherapy Combination to Bypass the Cold Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma.Frontiers in oncology · 2022Review
- Metronomic Anti-Cancer Therapy: A Multimodal Therapy Governed by the Tumor Microenvironment.Cancers · 2021Review
- Targeting hypoxic tumor microenvironment in pancreatic cancer.Journal of hematology & oncology · 2021Review
- Pharmacokinetics of gemcitabine and its amino acid ester prodrug following intravenous and oral administrations in mice.Biochemical pharmacology · 2020Article
- Review
- Chemotherapy response of pancreatic cancer by diffusion-weighted imaging (DWI) and intravoxel incoherent motion DWI (IVIM-DWI) in an orthotopic mouse model.Magma (New York, N.Y.) · 2019Article
- Review
- Article
- Role of vascular normalization in benefit from metronomic chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Combinatorial and sequential delivery of gemcitabine and oseltamivir phosphate from implantable poly(d,l-lactic-co-glycolic acid) cylinders disables human pancreatic cancer cell survival.Drug design, development and therapy · 2017Article
Corrections and comments
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13 authors.
Funding
Abstract
backgroundMetronomic chemotherapy has shown promising activity against solid tumors and is believed to act in an antiangiogenic manner. The current study describes and quantifies the therapeutic efficacy, and mode of activity, of metronomic gemcitabine and a dedicated antiangiogenic agent (DC101) in patient-derived xenografts of pancreatic cancer.
methodsTwo primary human pancreatic cancer xenograft lines were dosed metronomically with gemcitabine or DC101 weekly. Changes in tumor growth, vascular function, and metabolism over time were measured with magnetic resonance imaging, positron emission tomography, and immunofluorescence microscopy to determine the anti-tumor effects of the respective treatments.
resultsTumors treated with metronomic gemcitabine were 10-fold smaller than those in the control and DC101 groups. Metronomic gemcitabine, but not DC101, reduced the tumors' avidity for glucose, proliferation, and apoptosis. Metronomic gemcitabine-treated tumors had higher perfusion rates and uniformly distributed blood flow within the tumor, whereas perfusion rates in DC101-treated tumors were lower and confined to the periphery. DC101 treatment reduced the tumor's vascular density, but did not change their function. In contrast, metronomic gemcitabine increased vessel density, improved tumor perfusion transiently, and decreased hypoxia.
conclusionThe aggregate data suggest that metronomic gemcitabine treatment affects both tumor vasculature and tumor cells continuously, and the overall effect is to significantly slow tumor growth. The observed increase in tumor perfusion induced by metronomic gemcitabine may be used as a therapeutic window for the administration of a second drug or radiation therapy. Non-invasive imaging could be used to detect early changes in tumor physiology before reductions in tumor volume were evident.
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