Browsing by Subject "DFMO"

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    Eflornithine for the Chemoprevention of Luminal Gastrointestinal Neoplasms: A Systematic Review
    (Elmer Press, 2025) Godoy, Ambar; Montalvan-Sanchez, Daniela; Principe-Meneses, Fortunato S.; Riva-Moscoso, Adrian; Sierra, Leandro; Erazo, Gloria; Avila, Carlos; Ramirez-Rojas, Mirian; Giron, Roberto; Guifarro, Daniel A.; Medicine, School of Medicine
    Background: Gastrointestinal (GI) tract malignancies represent a significant global health burden, being major contributors to cancer-related morbidity and mortality globally, with over 7.7 million cases reported. While aspirin is a well-studied chemopreventive agent for GI neoplasms, its use may be limited due to the underlying bleeding risk. Eflornithine (DFMO) is an inhibitor of the ornithine decarboxylase (ODC) which inhibits polyamine synthesis, and has shown promise as an alternative chemopreventive agent, particularly in animal studies and limited clinical trials. Methods: Following PRISMA guidelines, we conducted a systematic review of studies evaluating DFMO alone or in combination for chemoprevention in premalignant GI lesions including chronic gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia. The protocol was registered in Prospero (CRD42022309307). Randomized controlled trials (RCTs) and cohort studies in English or Spanish were included. Results: Nine studies (six RCTs and three phase I-II trials) met inclusion criteria. Phase I-II trials involving Barrett's esophagus and gastric cancer did not report significant benefits. Phase III-IV trials combining DFMO with nonsteroidal anti-inflammatory drugs (NSAIDs) were associated with reductions in adenoma recurrence, size, and polyamine levels in high-risk GI cancer populations. Side effects included ototoxicity, reversible upon discontinuation, and mild GI events, both occurring at higher doses. Conclusion: While aspirin remains a frontline chemopreventive agent for GI neoplasms, this review shows that phase III-IV trials suggest promising outcomes in combination with NSAIDs, warranting further investigation. Notably, DFMO's low cost and favorable toxicity profile may position it as a viable alternative, emphasizing the need for additional RCTs to delineate its efficacy and safety in GI cancer prevention. Further investigation into DFMO's optimal dosage, duration, and side effect management is essential to establish it as a safe and effective chemopreventive agent.
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    Targeting polyamine biosynthesis to stimulate beta cell regeneration in zebrafish
    (Taylor & Francis, 2020-07-25) Robertson, Morgan A.; Padgett, Leah R.; Fine, Jonathan A.; Chopra, Gaurav; Mastracci, Teresa L.; Biology, School of Science
    Type 1 diabetes (T1D) is a disease characterized by destruction of the insulin-producing beta cells. Currently, there remains a critical gap in our understanding of how to reverse or prevent beta cell loss in individuals with T1D. Previous studies in mice discovered that pharmacologically inhibiting polyamine biosynthesis using difluoromethylornithine (DFMO) resulted in preserved beta cell function and mass. Similarly, treatment of non-obese diabetic mice with the tyrosine kinase inhibitor Imatinib mesylate reversed diabetes. The promising findings from these animal studies resulted in the initiation of two separate clinical trials that would repurpose either DFMO (NCT02384889) or Imatinib (NCT01781975) and determine effects on diabetes outcomes; however, whether these drugs directly stimulated beta cell growth remained unknown. To address this, we used the zebrafish model system to determine pharmacological impact on beta cell regeneration. After induction of beta cell death, zebrafish embryos were treated with either DFMO or Imatinib. Neither drug altered whole-body growth or exocrine pancreas length. Embryos treated with Imatinib showed no effect on beta cell regeneration; however, excitingly, DFMO enhanced beta cell regeneration. These data suggest that pharmacological inhibition of polyamine biosynthesis may be a promising therapeutic option to stimulate beta cell regeneration in the setting of diabetes.