Osteosarcoma is an aggressive malignant bone sarcoma common among children,adolescents,and young adults.Approximately 20%of patients present with pulmonary metastasis,and an additional 40%develop pulmonary osteosarcom...Osteosarcoma is an aggressive malignant bone sarcoma common among children,adolescents,and young adults.Approximately 20%of patients present with pulmonary metastasis,and an additional 40%develop pulmonary osteosarcoma later.The survival outcome in patients with recurrent osteosarcoma and pulmonary osteosarcoma has not improved overmany decades[1].展开更多
Sickle cell disease （SCD） is an inherited disorder of hemoglobin in which the abnormal hemoglobin S polymerizes when deoxygenated. This polymerization of hemoglobin S not only results in hemolysis and vaso- occlusio...Sickle cell disease （SCD） is an inherited disorder of hemoglobin in which the abnormal hemoglobin S polymerizes when deoxygenated. This polymerization of hemoglobin S not only results in hemolysis and vaso- occlusion but also precipitates inflammation, oxidative stress and chronic organ dysfunction. Oxidative stress is increasingly recognized as an important intermediate in these pathophysiological processes and is therefore an important target for therapeutic intervention. The transcription factor nuclear erythroid derived- 2 related factor 2 （Nrf2） controls the expression of anti-oxidant enzymes and is emerging as a protein whose function can be exploited with therapeutic intent. This review article is focused on triterpenoids that activate Nrf2, and their potential for reducing oxidative stress in SCD as an approach to prevent organ dysfunction associated with this disease. A brief overview of oxidative stress in the clinical context of SCD is accompanied by a discussion of several pathophysiological mechanisms contributing to oxidative stress. Finally, these mechanisms are then related to current management strategies in SCD that are either utilized currently or under evaluation. The article concludes with a perspective on the potential of the various therapeutic interventions to reduce oxidative stress and morbidity associated with SCD.展开更多
基金supported by the National Cancer Institute(R03CA273468,R03CA259901,P30CA043703,T32GM007250,T32CA059366,and K12CA076917)St.Baldrick’s Foundation,Hyundai Hope-on-Wheels Scholar Hope Grant,Andrew McDonough B+Foundation,Curing Kids Cancer,MIB Agents,Sarcoma Foundation of America,Sam Day Foundation,Children’s Cancer Research Fund,Center for Pediatric Immunotherapy at Rainbow,and a sponsored research agreement from MedPacto,Inc.who provided vactosertib for both in vitro and in vivo experiments.
文摘Osteosarcoma is an aggressive malignant bone sarcoma common among children,adolescents,and young adults.Approximately 20%of patients present with pulmonary metastasis,and an additional 40%develop pulmonary osteosarcoma later.The survival outcome in patients with recurrent osteosarcoma and pulmonary osteosarcoma has not improved overmany decades[1].
文摘Sickle cell disease （SCD） is an inherited disorder of hemoglobin in which the abnormal hemoglobin S polymerizes when deoxygenated. This polymerization of hemoglobin S not only results in hemolysis and vaso- occlusion but also precipitates inflammation, oxidative stress and chronic organ dysfunction. Oxidative stress is increasingly recognized as an important intermediate in these pathophysiological processes and is therefore an important target for therapeutic intervention. The transcription factor nuclear erythroid derived- 2 related factor 2 （Nrf2） controls the expression of anti-oxidant enzymes and is emerging as a protein whose function can be exploited with therapeutic intent. This review article is focused on triterpenoids that activate Nrf2, and their potential for reducing oxidative stress in SCD as an approach to prevent organ dysfunction associated with this disease. A brief overview of oxidative stress in the clinical context of SCD is accompanied by a discussion of several pathophysiological mechanisms contributing to oxidative stress. Finally, these mechanisms are then related to current management strategies in SCD that are either utilized currently or under evaluation. The article concludes with a perspective on the potential of the various therapeutic interventions to reduce oxidative stress and morbidity associated with SCD.
