ArticleCarcinogenesis2012
Evaluation of a mucoadhesive fenretinide patch for local intraoral delivery: a strategy to reintroduce fenretinide for oral cancer chemoprevention.
Article in Carcinogenesis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07149220 (Safety and Chemopreventive Efficacy of Fenretinide Mucoadhesive System in Subjects With Premalignant Oral Intraepithelial Neoplasia), which is not on this map. Cited by 13 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.
Safety and Chemopreventive Efficacy of Fenretinide Mucoadhesive System in Subjects With Premalignant Oral Intraepithelial Neoplasia (OIN) Lesions: In Conjunction With Pharmacokinetic Assessment in Healthy Subjects.
Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Advanced drug delivery systems for oral squamous cell carcinoma: a comprehensive review of nanotechnology-based and other innovative approaches.Frontiers in drug delivery · 2025Review
- Growth modulatory effects of fenretinide encompass keratinocyte terminal differentiation: a favorable outcome for oral squamous cell carcinoma chemoprevention.Carcinogenesis · 2024Article
- Article
- Pharmacokinetic Model Analysis of Supralingual, Oral and Intravenous Deliveries of Mycophenolic Acid.Pharmaceutics · 2021Article
- Microencapsulation of amorphous solid dispersions of fenretinide enhances drug solubility and release from PLGA in vitro and in vivo.International journal of pharmaceutics · 2020Article
- Pharmacokinetic and Metabolic Profiling of Key Active Components of Dietary SupplementJournal of agricultural and food chemistry · 2020Article
- Fenretinide, Tocilizumab, and Reparixin Provide Multifaceted Disruption of Oral Squamous Cell Carcinoma Stem Cell Properties: Implications for Tertiary Chemoprevention.Molecular cancer therapeutics · 2019Article
- In vivo controlled release of fenretinide from long-acting release depots for chemoprevention of oral squamous cell carcinoma recurrence.International journal of pharmaceutics · 2018Article
- Plasma concentration of metformin and dexamethasone after administration through Osseogate.Drug delivery · 2017Article
- Fenretinide: A Potential Treatment for Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2016Article
- Fenretinide Perturbs Focal Adhesion Kinase in Premalignant and Malignant Human Oral Keratinocytes. Fenretinide's Chemopreventive Mechanisms Include ECM Interactions.Cancer prevention research (Philadelphia, Pa.) · 2015Article
- Widefield optical imaging of changes in uptake of glucose and tissue extracellular pH in head and neck cancer.Cancer prevention research (Philadelphia, Pa.) · 2014Article
- Combination of fenretinide and selenite inhibits proliferation and induces apoptosis in ovarian cancer cells.International journal of molecular sciences · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Systemic delivery of fenretinide in oral cancer chemoprevention trials has been largely unsuccessful due to dose-limiting toxicities and subtherapeutic intraoral drug levels. Local drug delivery, however, provides site-specific therapeutically relevant levels while minimizing systemic exposure. These studies evaluated the pharmacokinetic and growth-modulatory parameters of fenretinide mucoadhesive patch application on rabbit buccal mucosa. Fenretinide and blank-control patches were placed on right/left buccal mucosa, respectively, in eight rabbits (30 min, q.d., 10 days). No clinical or histological deleterious effects occurred. LC-MS/MS analyses of post-treatment samples revealed a delivery gradient with highest fenretinide levels achieved at the patch-mucosal interface (no metabolites), pharmacologically active levels in fenretinide-treated oral mucosa (mean: 5.65 μM; trace amounts of 4-oxo-4-HPR) and undetectable sera levels. Epithelial markers for cell proliferation (Ki-67), terminal differentiation (transglutaminase 1-TGase1) and glucuronidation (UDP-glucuronosyltransferase1A1-UGT1A1) exhibited fenretinide concentration-specific relationships (elevated TGase1 and UGT1A1 levels <5 μM, reduced Ki-67 indices >5 μM) relative to blank-treated epithelium. All fenretinide-treated tissues showed significantly increased intraepithelial apoptosis (TUNEL) positivity, implying activation of intersecting apoptotic and differentiation pathways. Human oral mucosal correlative studies showed substantial interdonor variations in levels of the enzyme (cytochrome P450 3A4-CYP3A4) responsible for conversion of fenretinide to its highly active metabolite, 4-oxo-4-HPR. Complementary in vitro assays in human oral keratinocytes revealed fenretinide and 4-oxo-4-HPR's preferential suppression of DNA synthesis in dysplastic as opposed to normal oral keratinocytes. Collectively, these data showed that mucoadhesive patch-mediated fenretinide delivery is a viable strategy to reintroduce a compound known to induce keratinocyte differentiation to human oral cancer chemoprevention trials.
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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.