Inflammatory myofibroblastic tumor(IMT)is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate.Diagnostic challenges arise from the diverse pathological pre...Inflammatory myofibroblastic tumor(IMT)is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate.Diagnostic challenges arise from the diverse pathological presentation,variable symptomatology,and lack of different imaging features.However,IMT is identified by the fusion of the anaplastic lymphoma kinase(ALK)gene,which is present in approximately 70%of cases,with various fusion partners,including ran-binding protein 2(RANBP2),which allows confirmation of the diagnosis.While surgery is the preferred approach for localized tumors,the optimal long-term treatment for advanced or metastatic disease is difficult to define.Targeted therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in IMT.Crizotinib,an ALK tyrosine kinase inhibitor(TKI),was officially approved by the US Food and Drug Administration(FDA)in 2020 to treat IMT with ALK rearrangement.However,most patients face resistance and disease progression,requiring consideration of sequential treatments.Combining radiotherapy with targeted therapy appears to be beneficial in this indication.Early promising results have also been achieved with immunotherapy,indicating potential for combined therapy approaches.However,defined recommendations are still lacking.This review analyzes the available research on IMT,including genetic disorders and their impact on the course of the disease,data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication,as well as summarizing general knowledge about prognostic and predictive factors,also in terms of resistance to systemic therapy.展开更多
Objectives:Caveolin-3(Cav-3)plays a pivotal role in maintaining skeletal muscle mass and function.Mutations ordeletions of Cav-3 can result in the development of variousforms of myopathy,which affect the integrity and...Objectives:Caveolin-3(Cav-3)plays a pivotal role in maintaining skeletal muscle mass and function.Mutations ordeletions of Cav-3 can result in the development of variousforms of myopathy,which affect the integrity and repaircapacity of musclefiber membranes.However,the potentialeffect of Cav-3 on myofiber type composition remainsunclear.Methods:To investigate the effect of Cav-3 on musclestrength and running capacity,we examined the grip forcetest and the low/high-speed running test.Oxidative andglycolytic myofiber-related genes,proteins,and skeletalmusclefiber composition were measured to determine therole of the Cav-3 in oxidative myofiber formation.Results:We report the impact of Cav-3 on enhancing muscleendurance performance in female mice,and the discovery ofa new physiological function to increase the proportion ofslow-twitch oxidative musclefiber by analyzing thegastrocnemius and soleus.Skeletal muscle-specific ablationof Cav-3 in female mice increased oxidative myofiber-relatedgene expression and type I oxidative myofiber composition,with resultant improvements in endurance performance.Inmale mice,the absence of Cav-3 in skeletal muscle reduced inthe expression of glycolyticfiber-related genes and proteins.Conclusions:This study identified Cav-3 as a regulatorof slow-twitch oxidative musclefiber formation acting onfemale mice,which may provide a potential target forimproving muscle oxidative function.展开更多
基金National Science Center 2019/35/O/NZ2/03761(AMC)。
文摘Inflammatory myofibroblastic tumor(IMT)is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate.Diagnostic challenges arise from the diverse pathological presentation,variable symptomatology,and lack of different imaging features.However,IMT is identified by the fusion of the anaplastic lymphoma kinase(ALK)gene,which is present in approximately 70%of cases,with various fusion partners,including ran-binding protein 2(RANBP2),which allows confirmation of the diagnosis.While surgery is the preferred approach for localized tumors,the optimal long-term treatment for advanced or metastatic disease is difficult to define.Targeted therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in IMT.Crizotinib,an ALK tyrosine kinase inhibitor(TKI),was officially approved by the US Food and Drug Administration(FDA)in 2020 to treat IMT with ALK rearrangement.However,most patients face resistance and disease progression,requiring consideration of sequential treatments.Combining radiotherapy with targeted therapy appears to be beneficial in this indication.Early promising results have also been achieved with immunotherapy,indicating potential for combined therapy approaches.However,defined recommendations are still lacking.This review analyzes the available research on IMT,including genetic disorders and their impact on the course of the disease,data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication,as well as summarizing general knowledge about prognostic and predictive factors,also in terms of resistance to systemic therapy.
文摘Objectives:Caveolin-3(Cav-3)plays a pivotal role in maintaining skeletal muscle mass and function.Mutations ordeletions of Cav-3 can result in the development of variousforms of myopathy,which affect the integrity and repaircapacity of musclefiber membranes.However,the potentialeffect of Cav-3 on myofiber type composition remainsunclear.Methods:To investigate the effect of Cav-3 on musclestrength and running capacity,we examined the grip forcetest and the low/high-speed running test.Oxidative andglycolytic myofiber-related genes,proteins,and skeletalmusclefiber composition were measured to determine therole of the Cav-3 in oxidative myofiber formation.Results:We report the impact of Cav-3 on enhancing muscleendurance performance in female mice,and the discovery ofa new physiological function to increase the proportion ofslow-twitch oxidative musclefiber by analyzing thegastrocnemius and soleus.Skeletal muscle-specific ablationof Cav-3 in female mice increased oxidative myofiber-relatedgene expression and type I oxidative myofiber composition,with resultant improvements in endurance performance.Inmale mice,the absence of Cav-3 in skeletal muscle reduced inthe expression of glycolyticfiber-related genes and proteins.Conclusions:This study identified Cav-3 as a regulatorof slow-twitch oxidative musclefiber formation acting onfemale mice,which may provide a potential target forimproving muscle oxidative function.
