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View article: Supplementary Figure S4 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Figure S4 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
Supplementary Figure S4: DFMO inhibits sarcosphere formation. Quantification of the data presented in Figure 2. The indicated cells were grown in non-adherent conditions with non-differentiating media and treated with the indicated concent…
View article: Supplementary Figure S5 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Figure S5 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
Supplementary Figure S5: 1% DFMO does not prevent tumor growth. Fragments of the JHHESX3 PDX were implanted either in the pretibial space (orthotopic; panel A) or subcutaneously (B) in 10 NSG mice, and mice were randomly assigned to regula…
View article: Supplementary Figure S11 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Figure S11 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
Supplementary Figure S11: Gene expression changes induced by DFMO. Volcano plot showing genes differentially expressed between tumors in control mice and tumors in DFMO-treated mice. The Log2 Fold Change indicates the mean relative express…
View article: Supplementary Table S3 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Table S3 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
The top 500 most differentially expressed genes between tumors from control mice and tumors from DFMO-treated mice
View article: Supplementary Figure S3 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Figure S3 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
Supplementary Figure S3: DFMO causes a cell cycle arrest. Histograms demonstrate the percentage of TC71 cells (A) and SK-ES-1 cells (C) in the G1 (purple), S (yellow), and G2/M (green) phases of the cell cycle in control cultures and in cu…
View article: Supplementary Figure S8 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Figure S8 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
Supplementary Figure S8: DFMO induces lipid peroxidation. Twenty thousand MHH-ES1 cells (A and B) or SK-ES1 cells (C and D) were plated in ultra-low attachment plates and treated with (B and D) or without (A and C) 5 mM DFMO. After 24 hour…
View article: Data from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Data from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
Purpose:Despite decades of clinical trials, no progress has been made in improving the survival of patients with Ewing sarcoma who either present with metastatic disease or suffer a metastatic relapse. In our preclinical models, we found d…
View article: Supplementary Figure S6 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Figure S6 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
Supplementary Figure S6: 2% DFMO diminishes polyamine production in vivo. Fragments of the JHHESX3 PDX were implanted in NSG mice either subcutaneously or in the tibia (orthotopic) and mice were randomly assigned to receive either regular …
View article: Supplementary Table S1 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Table S1 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
The top 500 most variably expressed genes between bone marrow and lung
View article: Supplementary Figure S2 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Figure S2 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
Supplementary Figure S2: Ewing sarcoma cells after DFMO treatment. Photomicrographs of MHH-ES1 (A), TC71 (B) and SK-ES-1 (C) cells captured by the Incucyte camera after 4 days of treatment with 1 mM DFMO, prior to washout as described in F…
View article: Supplementary Table S2 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Table S2 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
The top 500 differentially expressed genes between primary tumor/bone marrow and lungs
View article: Supplementary Figure S7 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Figure S7 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
Supplementary Figure S7: DFMO does not induce caspase activity. 300,000 MHH-ES1 cells (A) or SK-ES1 cells (B) were plated in RPMI + 10% FBS. After 24 hours, the media was removed, and fresh media supplemented with Incucyte Caspase-3/7 Dye …
View article: Supplementary Figure S1 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Figure S1 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
Supplementary Figure S1: DFMO inhibits Ewing sarcoma proliferation in vitro. TC71 cells (A) and SK-ES-1 cells (D) were treated with DFMO at various concentrations. Error bars represent 95% confidence interval for triplicate evaluation of e…
View article: Supplementary Figure S9 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Figure S9 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
Supplementary Figure S9: DFMO-mediated inhibition of sarcosphere formation is rescued by inhibitors of ferroptosis but not by inhibition of apoptosis. MHH-ES1 cells (A) and SK-ES1 cells (B) were grown in non-adherent conditions with non-di…
View article: Supplementary Figure S10 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Supplementary Figure S10 from Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
Supplementary Figure S10: Dissemination of Ewing sarcoma tumor cells alters the expression of multiple ferroptosis-related genes. Normalized read counts of key genes from the RNA-seq experiment described in Figure 5. In brief, tumors compo…
View article: Androgen receptor drives polyamine synthesis creating a vulnerability for prostate cancer
Androgen receptor drives polyamine synthesis creating a vulnerability for prostate cancer Open
Supraphysiological androgen (SPA) treatment can paradoxically restrict growth of castration-resistant prostate cancer with high androgen receptor (AR) activity, which is the basis for use of Bipolar Androgen Therapy (BAT) for patients with…
View article: The Synergistic Benefit of Combination Strategies Targeting Tumor Cell Polyamine Homeostasis
The Synergistic Benefit of Combination Strategies Targeting Tumor Cell Polyamine Homeostasis Open
Mammalian polyamines, including putrescine, spermidine, and spermine, are positively charged amines that are essential for all living cells including neoplastic cells. An increasing understanding of polyamine metabolism, its molecular func…
View article: Polyamine Depletion by D, L-alpha-difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
Polyamine Depletion by D, L-alpha-difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis Open
A bstract Polyamine metabolism and signaling play important roles in multiple cancers but have not previously been studied in Ewing sarcoma. Here, we show that blocking polyamine synthesis with D, L-alpha-difluoromethylornithine (DFMO) cau…
View article: The Polyamine Analogue Ivospemin Increases Chemotherapeutic Efficacy in Murine Ovarian Cancer
The Polyamine Analogue Ivospemin Increases Chemotherapeutic Efficacy in Murine Ovarian Cancer Open
Polyamines are small polycationic alkylamines that are absolutely required for the continual growth and proliferation of cancer cells. The polyamine analogue ivospemin, also known as SBP-101, has shown efficacy in slowing pancreatic and ov…
View article: Polyamines: the pivotal amines in influencing the tumor microenvironment
Polyamines: the pivotal amines in influencing the tumor microenvironment Open
View article: Reduction of spermine synthase enhances autophagy to suppress Tau accumulation
Reduction of spermine synthase enhances autophagy to suppress Tau accumulation Open
View article: Polyamine Catabolism and Its Role in Renal Injury and Fibrosis in Mice Subjected to Repeated Low-Dose Cisplatin Treatment
Polyamine Catabolism and Its Role in Renal Injury and Fibrosis in Mice Subjected to Repeated Low-Dose Cisplatin Treatment Open
Cisplatin, a chemotherapeutic agent, can cause nephrotoxic and ototoxic injuries. Using a mouse model of repeated low dose cisplatin (RLDC), we compared the kidneys of cisplatin- and vehicle-treated mice on days 3 (early injury phase) and …
View article: Impaired polyamine metabolism causes behavioral and neuroanatomical defects in a mouse model of Snyder–Robinson syndrome
Impaired polyamine metabolism causes behavioral and neuroanatomical defects in a mouse model of Snyder–Robinson syndrome Open
Snyder–Robinson syndrome (SRS) is a rare X-linked recessive disorder caused by a mutation in the SMS gene, which encodes spermine synthase, and aberrant polyamine metabolism. SRS is characterized by intellectual disability, thin habitus, s…
View article: Effects of Spermine Synthase Deficiency in Mesenchymal Stromal Cells Are Rescued by Upstream Inhibition of Ornithine Decarboxylase
Effects of Spermine Synthase Deficiency in Mesenchymal Stromal Cells Are Rescued by Upstream Inhibition of Ornithine Decarboxylase Open
Despite the well-known relevance of polyamines to many forms of life, little is known about how polyamines regulate osteogenesis and skeletal homeostasis. Here, we report a series of in vitro studies conducted with human-bone-marrow-derive…
View article: Snyder-Robinson syndrome presenting with learning disability, epilepsy, and osteoporosis: A novel SMS gene variant
Snyder-Robinson syndrome presenting with learning disability, epilepsy, and osteoporosis: A novel SMS gene variant Open
View article: Polyamine transport inhibition and cisplatin synergistically enhance tumor control through oxidative stress in murine head and neck cancer models
Polyamine transport inhibition and cisplatin synergistically enhance tumor control through oxidative stress in murine head and neck cancer models Open
Background: Surgery and/or platinum-based chemoradiation remain standard of care for patients with head and neck squamous cell carcinoma (HNSCC). While these therapies are effective in a subset of patients, a substantial proportion experie…
View article: Difluoromethylornithine rebalances aberrant polyamine ratios in <scp>Snyder–Robinson</scp> syndrome
Difluoromethylornithine rebalances aberrant polyamine ratios in <span>Snyder–Robinson</span> syndrome Open
View article: Editorial to the Special Issue on “Polyamine Metabolism in Health and Disease: Potential for Polyamine-Targeted Therapies and Prevention”
Editorial to the Special Issue on “Polyamine Metabolism in Health and Disease: Potential for Polyamine-Targeted Therapies and Prevention” Open
To introduce this Special Issue, I refer the reader to the timely review by Zahedi and colleagues [...]
View article: Polyamine transport inhibition and cisplatin synergistically enhance tumor control through oxidative stress in murine head and neck cancer models
Polyamine transport inhibition and cisplatin synergistically enhance tumor control through oxidative stress in murine head and neck cancer models Open
Background Surgery and/or platinum-based chemoradiation remain standard of care for patients with head and neck squamous cell carcinoma (HNSCC). While these therapies are effective in a subset of patients, a substantial proportion experien…
View article: Deoxyhypusine synthase mutations alter the post-translational modification of eukaryotic initiation factor 5A resulting in impaired human and mouse neural homeostasis
Deoxyhypusine synthase mutations alter the post-translational modification of eukaryotic initiation factor 5A resulting in impaired human and mouse neural homeostasis Open
DHPS deficiency is a rare genetic disease caused by biallelic hypomorphic variants in the Deoxyhypusine synthase (DHPS) gene. The DHPS enzyme functions in mRNA translation by catalyzing the post-translational modification, an…