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Discordant Effects of Polyamine Depletion by DENSpm and DFMO on β-cell Cytokine Stress and Diabetes Outcomes in Mice.
Endocrinology
January 2024
Department of Pediatrics, The University of Chicago, Chicago, IL 60637, USA.
Type 1 diabetes (T1D) is an autoimmune disease leading to dysfunction and loss of insulin-secreting β cells. In β cells, polyamines have been implicated in causing cellular stress and dysfunction. An inhibitor of polyamine biosynthesis, difluoromethylornithine (DFMO), has been shown to delay T1D in mouse models and preserve β-cell function in humans with recent-onset T1D.
View Article and Find Full Text PDFChemoprevention of Colon Cancer by DFMO, Sulindac, and NO-Sulindac Administered Individually or in Combinations in F344 Rats.
Cancers (Basel)
August 2023
Center for Cancer Prevention and Drug Development, Department of Internal Medicine, Hem-Onc Section, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Non-steroidal anti-inflammatory drugs (NSAIDs) are promising colorectal cancer (CRC) chemopreventive drugs; however, to overcome NSAIDs' associated side effects, there is a need to develop safer and efficacious approaches. The present study was designed to evaluate (i) the efficacy of nitric-oxide releasing (NO)-Sulindac as compared to Sulindac; (ii) whether NO-Sulindac is superior to Sulindac in enhancing low-dose difluoromethylornithine (DFMO)-induced chemopreventive efficacy, and (iii) assessing the key biomarkers associated with colon tumor inhibition by these combinations. In F344 rats, colonic tumors were induced by azoxymethane (AOM).
View Article and Find Full Text PDFMultifunctionalized Gold Sub-Nanometer Particles for Sensitizing Radiotherapy against Glioblastoma.
Small
February 2021
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
Glioblastoma is the most common lethal malignant intracranial tumor with a low 5-year survival rate. Currently, the maximal safe surgical resection, followed by high-dose radiotherapy (RT), is a standard treatment for glioblastoma. However, high-dose radiation to the brain is associated with brain injury and results in a high fatality rate.
View Article and Find Full Text PDFPotentiating NK cell activity by combination of Rosuvastatin and Difluoromethylornithine for effective chemopreventive efficacy against Colon Cancer.
Sci Rep
November 2016
Center for Cancer Prevention and Drug Development, Department of Medicine, Hematology Oncology Section, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Colorectal cancer (CRC) is the second highest cause of cancer-related deaths. A successful strategy to improve chemopreventive efficacies is by down-regulating tumor polyamines and enhancing NK cell activities. Colonic carcinogenesis was induced by azoxymethane (AOM) in male F344 rats.
View Article and Find Full Text PDFEfficacy and safety of eflornithine (CPP-1X)/sulindac combination therapy versus each as monotherapy in patients with familial adenomatous polyposis (FAP): design and rationale of a randomized, double-blind, Phase III trial.
BMC Gastroenterol
August 2016
Cancer Prevention Pharmaceuticals, Inc., 1760 E. River Rd, Tucson, AZ, 85718, USA.
Background: Molecular studies suggest inhibition of colorectal mucosal polyamines (PAs) may be a promising approach to prevent colorectal cancer (CRC). Inhibition of ornithine decarboxylase (ODC) using low-dose eflornithine (DFMO, CPP-1X), combined with maximal PA export using low-dose sulindac, results in greatly reduced levels of normal mucosal PAs. In a clinical trial, this combination (compared with placebo) reduced the 3-year incidence of subsequent high-risk adenomas by >90 %.
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