ArticleClinical cancer research : an official journal of the American Association for Cancer Research2008
Targeted inhibition of cyclic AMP phosphodiesterase-4 promotes brain tumor regression.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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66 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
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- A New Adjuvant Treatment for Glioblastoma Using Aprepitant, Vortioxetine, Roflumilast and Olanzapine: The AVRO Regimen.International journal of molecular sciences · 2025Review
- The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy.Frontiers in immunology · 2025Review
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- Inhibition of autophagy and induction of glioblastoma cell death by NEO214, a perillyl alcohol-rolipram conjugate.Autophagy · 2023Article
- Once upon a Testis: The Tale of Cyclic Nucleotide Phosphodiesterase in Testicular Cancers.International journal of molecular sciences · 2023Review
- Repurposing autophagy regulators in brain tumors.International journal of cancer · 2022Review
- Review
- Prioritization and functional analysis of GWAS risk loci for Barrett's esophagus and esophageal adenocarcinoma.Human molecular genetics · 2022Article
- Clinical Implication of Phosphodiesterase-4-Inhibition.International journal of molecular sciences · 2022Review
- The Monoterpenoid Perillyl Alcohol: Anticancer Agent and Medium to Overcome Biological Barriers.Pharmaceutics · 2021Review
- Suppression of Proliferation of Human Glioblastoma Cells by Combined Phosphodiesterase and Multidrug Resistance-Associated Protein 1 Inhibition.International journal of molecular sciences · 2021Article
- Eggmanone Effectively Overcomes Prostate Cancer Cell Chemoresistance.Biomedicines · 2021Article
- A functional variant on 20q13.33 related to glioma risk alters enhancer activity and modulates expression of multiple genes.Human mutation · 2021Article
- The Role of Epac in Cancer Progression.International journal of molecular sciences · 2020Review
6 more citing papers are in PubMed but not listed here.
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9 authors at 5 institutions in 3 countries.
Funding
Abstract
purposeAs favorable outcomes from malignant brain tumors remain limited by poor survival and treatment-related toxicity, novel approaches to cure are essential. Previously, we identified the cyclic AMP phosphodiesterase-4 (PDE4) inhibitor Rolipram as a potent antitumor agent. Here, we investigate the role of PDE4 in brain tumors and examine the utility of PDE4 as a therapeutic target. EXPERIMENTAL
designImmunohistochemistry was used to evaluate the expression pattern of a subfamily of PDE4, PDE4A, in multiple brain tumor types. To evaluate the effect of PDE4A on growth, a brain-specific isoform, PDE4A1 was overexpressed in xenografts of Daoy medulloblastoma and U87 glioblastoma cells. To determine therapeutic potential of PDE4 inhibition, Rolipram, temozolomide, and radiation were tested alone and in combination on mice bearing intracranial U87 xenografts.
resultsWe found that PDE4A is expressed in medulloblastoma, glioblastoma, oligodendroglioma, ependymoma, and meningioma. Moreover, when PDE4A1 was overexpressed in Daoy medulloblastoma and U87 glioblastoma cells, in vivo doubling times were significantly shorter for PDE4A1-overexpressing xenografts compared with controls. In long-term survival and bioluminescence studies, Rolipram in combination with first-line therapy for malignant gliomas (temozolomide and conformal radiation therapy) enhanced the survival of mice bearing intracranial xenografts of U87 glioblastoma cells. Bioluminescence imaging indicated that whereas temozolomide and radiation therapy arrested intracranial tumor growth, the addition of Rolipram to this regimen resulted in tumor regression.
conclusionsThis study shows that PDE4 is widely expressed in brain tumors and promotes their growth and that inhibition with Rolipram overcomes tumor resistance and mediates tumor regression.
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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.