Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer...Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.展开更多
Osteosarcoma(OS)is the most common type of bone sarcoma.Despite the availability of multimodal treatment with surgery and chemotherapy,the clinical results remain unsatisfactory.The main reason for the poor outcomes i...Osteosarcoma(OS)is the most common type of bone sarcoma.Despite the availability of multimodal treatment with surgery and chemotherapy,the clinical results remain unsatisfactory.The main reason for the poor outcomes in patients with OS is the development of resistance to methotrexate,cisplatin,doxorubicin,and ifosfamide.Molecular and cellular mechanisms associated with resistance to chemotherapy include DNA repair and cell-cycle alterations,enhanced drug efflux,increased detoxification,resistance to apoptosis,autophagy,tumor extracellular matrix,and angiogenesis.This versatility of cells to generate chemoresistance has motivated the use of anti-angiogenic therapy based on tyrosine kinase inhibitors.This approach has shown that other therapies,along with standard chemotherapy,can improve responses to therapy in patients with OS.Moreover,microRNAs may act as predictors of drug resistance in OS.This review provides insight into the molecular and cellular mechanisms involved in the development of resistance during the treatment of OS and discusses promising novel therapies(e.g.,afatinib and palbociclib)for overcoming resistance to chemotherapy in OS.展开更多
基金supported by FIS/IMSS project No.FIS/IMSS/PROT/G13/1216CGA received Beca de Excelencia en Investigación by Fundación IMSS,ACS+1 种基金JJSU received financial support from CIS/IMSSCONACy T,RPA received financial support from USC-CONACYT Postdoctoral Scholars Program
文摘Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.
文摘Osteosarcoma(OS)is the most common type of bone sarcoma.Despite the availability of multimodal treatment with surgery and chemotherapy,the clinical results remain unsatisfactory.The main reason for the poor outcomes in patients with OS is the development of resistance to methotrexate,cisplatin,doxorubicin,and ifosfamide.Molecular and cellular mechanisms associated with resistance to chemotherapy include DNA repair and cell-cycle alterations,enhanced drug efflux,increased detoxification,resistance to apoptosis,autophagy,tumor extracellular matrix,and angiogenesis.This versatility of cells to generate chemoresistance has motivated the use of anti-angiogenic therapy based on tyrosine kinase inhibitors.This approach has shown that other therapies,along with standard chemotherapy,can improve responses to therapy in patients with OS.Moreover,microRNAs may act as predictors of drug resistance in OS.This review provides insight into the molecular and cellular mechanisms involved in the development of resistance during the treatment of OS and discusses promising novel therapies(e.g.,afatinib and palbociclib)for overcoming resistance to chemotherapy in OS.
