fumarates and Osteosarcoma

Fumarate-containing pharmaceuticals are potent therapeutic agents that influence multiple cellular pathways. Despite proven clinical efficacy, there is a significant lack of data that directly defines the molecular mechanisms of action of related, yet distinct fumarate compounds. We systematically compared the impact of dimethyl fumarate (DMF), monomethyl fumarate (MMF) and a mixture of monoethyl fumarate salts (Ca(++), Mg(++), Zn(++); MEF) on defined cellular responses. We demonstrate that DMF inhibited NF-κB-driven cytokine production and nuclear translocation of p65 and p52 in an Nrf2-independent manner. Equivalent doses of MMF and MEF did not affect NF-κB signaling. These results highlight a key difference in the biological impact of related, yet distinct fumarate compounds.

Topics: Active Transport, Cell Nucleus; Animals; Bone Neoplasms; Burkitt Lymphoma; Cations; Cell Line, Tumor; Cells, Cultured; Cytokines; Dimethyl Fumarate; Fumarates; Humans; In Vitro Techniques; Lymphocytes; Maleates; Mice; Mice, Knockout; Molecular Structure; Neoplasm Proteins; NF-E2-Related Factor 2; NF-kappa B; NF-kappa B p52 Subunit; Osteosarcoma; Signal Transduction; Spleen; Transcription Factor RelA

Biodegradable and injectable hydroxy terminated-poly propylene fumarate (HT-PPF) bone cement was developed. The injectable formulation consisting HT-PPF and comonomer, n-vinyl pyrrolidone, calcium phosphate filler, free radical catalyst, accelerator and radiopaque agent sets rapidly to hard mass with low exothermic temperature. The candidate bone cement attains mechanical strength more than the required compressive strength of 5 MPa and compressive modulus 50 MPa. The candidate bone cement resin elicits cell adhesion and cytoplasmic spreading of osteoblast cells. The cured bone cement does not induce intracutaneous irritation and skin sensitization. The candidate bone cement is tissue compatible without eliciting any adverse tissue reactions. The candidate bone cement is osteoconductive and inductive and allow osteointegration and bone remodeling. HT-PPF bone cement is candidate bone cement for minimally invasive radiological procedures for the treatment of bone diseases and spinal compression fractures.

Topics: Biocompatible Materials; Biodegradation, Environmental; Biomechanical Phenomena; Body Fluids; Bone Cements; Bone Regeneration; Calcium Phosphates; Cell Adhesion; Cell Line, Tumor; Compressive Strength; Contrast Media; Cross-Linking Reagents; Fumarates; Guidelines as Topic; Hardness; Humans; Hydrogen-Ion Concentration; Injections; Materials Testing; Minimally Invasive Surgical Procedures; Molecular Structure; Orthopedic Procedures; Osseointegration; Osteoblasts; Osteosarcoma; Polypropylenes; Pyrrolidinones; Spectroscopy, Fourier Transform Infrared; Temperature

Topics: Acids; Arthritis; Arthritis, Rheumatoid; Breast Neoplasms; Chromatography; Citric Acid Cycle; Female; Fumarates; Glutarates; Histocytochemistry; Hodgkin Disease; Humans; Neoplasms; Osteosarcoma; Rectal Neoplasms; Sarcoma; Stomach Neoplasms; Stomach Ulcer; Succinates; Thyroid Neoplasms; Uric Acid; Urine; Uterine Cervical Neoplasms; Uterine Neoplasms