ArticleBrain research2008
PDE5 inhibitors enhance tumor permeability and efficacy of chemotherapy in a rat brain tumor model.
Article in Brain research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 113 citations in OpenAlex.
- Aildenafil citrate with superior PDE5 selectivity ameliorates cognitive and behavioral impairments in APP/PS1 Alzheimer's disease mice: a preclinical phenotypic study.Frontiers in pharmacology · 2026Article
- Revisiting strategies to target ABC transporter-mediated drug resistance in CNS cancer.Cancer biology & medicine · 2025Review
- Membrane-Mediated Action of Phosphodiesterase 5 Inhibitors.Pharmaceutics · 2025Article
- A novel phosphodiesterase target as a therapeutic approach: inhibiting DEN-induced hepatocellular carcinoma progression.EXCLI journal · 2025Review
- Endovascular surgical neuro-oncology: advancing a new subspecialty.Journal of neuro-oncology · 2024Review
- Signature reversion of three disease-associated gene signatures prioritizes cancer drug repurposing candidates.FEBS open bio · 2024Article
- Phase 2 Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma.medRxiv : the preprint server for health sciences · 2024Article
- Rethinking of phosphodiesterase 5 inhibition: the old, the new and the perspective in human health.Frontiers in endocrinology · 2024Review
- Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Low-intensity open-field blast exposure effects on neurovascular unit ultrastructure in mice.Acta neuropathologica communications · 2023Article
- Review
- Phosphodiesterase 5 inhibitor sildenafil potentiates the antitumor activity of cisplatin by ROS-mediated apoptosis: a role of deregulated glucose metabolism.Apoptosis : an international journal on programmed cell death · 2022Article
- How do phosphodiesterase-5 inhibitors affect cancer? A focus on glioblastoma multiforme.Pharmacological reports : PR · 2022Review
- Pros and Cons of Pharmacological Manipulation of cGMP-PDEs in the Prevention and Treatment of Breast Cancer.International journal of molecular sciences · 2021Review
- Role of phosphodiesterase 1 in the pathophysiology of diseases and potential therapeutic opportunities.Pharmacology & therapeutics · 2021Review
- The Potential Role of Sildenafil in Cancer Management through EPR Augmentation.Journal of personalized medicine · 2021Review
- Modulation of Blood-Brain Barrier Permeability by Activating Adenosine A2 Receptors in Oncological Treatment.Biomolecules · 2021Review
- Review
- Regulation of pathological blood-brain barrier for intracranial enhanced drug delivery and anti-glioblastoma therapeutics.Oncology research · 2021Review
- New Approaches in Oncology for Repositioning Drugs: The Case of PDE5 Inhibitor Sildenafil.Frontiers in oncology · 2021Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The blood-brain tumor barrier (BTB) significantly limits delivery of therapeutic concentrations of chemotherapy to brain tumors. A novel approach to selectively increase drug delivery is pharmacologic modulation of signaling molecules that regulate BTB permeability, such as those in cGMP signaling. Here we show that oral administration of sildenafil (Viagra) and vardenafil (Levitra), inhibitors of cGMP-specific PDE5, selectively increased tumor capillary permeability in 9L gliosarcoma-bearing rats with no significant increase in normal brain capillaries. Tumor-bearing rats treated with the chemotherapy agent, adriamycin, in combination with vardenafil survived significantly longer than rats treated with adriamycin alone. The selective increase in tumor capillary permeability appears to be mediated by a selective increase in tumor cGMP levels and increased vesicular transport through tumor capillaries, and could be attenuated by iberiotoxin, a selective inhibitor for calcium-dependent potassium (K(Ca)) channels, that are effectors in cGMP signaling. The effect by sildenafil could be further increased by simultaneously using another BTB "opener", bradykinin. Collectively, this data demonstrates that oral administration of PDE5 inhibitors selectively increases BTB permeability and enhances anti-tumor efficacy for a chemotherapeutic agent. These findings have significant implications for improving delivery of anti-tumor agents to brain tumors.
Indexed as
Identifiers
What OpenQuestion holds
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.