The liver is a unique parenchymal organ with a regenerative capacity allowing it to restore up to 70%of its volume.Although knowledge of this phenomenon dates back to Greek mythology(the story of Prometheus),many aspe...The liver is a unique parenchymal organ with a regenerative capacity allowing it to restore up to 70%of its volume.Although knowledge of this phenomenon dates back to Greek mythology(the story of Prometheus),many aspects of liver regeneration are still not understood.A variety of different factors,including inflammatory cytokines,growth factors,and bile acids,promote liver regeneration and control the final size of the organ during typical regeneration,which is performed by mature hepatocytes,and during alternative regeneration,which is performed by recently identified resident stem cells called“hepatic progenitor cells”.Hepatic progenitor cells drive liver regeneration when hepatocytes are unable to restore the liver mass,such as in cases of chronic injury or excessive acute injury.In liver maintenance,the body mass ratio is essential for homeostasis because the liver has numerous functions;therefore,a greater understanding of this process will lead to better control of liver injuries,improved transplantation of small grafts and the discovery of new methods for the treatment of liver diseases.The current review sheds light on the key molecular pathways and cells involved in typical and progenitor-dependent liver mass regeneration after various acute or chronic injuries.Subsequent studies and a better understanding of liver regeneration will lead to the development of new therapeutic methods for liver diseases.展开更多
Objective:Glioma is a highly invasive tumor,frequently disposed in essential areas of the brain,which makes its surgical excision extremely difficult;meanwhile adjuvant therapy remains quite ineffective.Methods:In the...Objective:Glioma is a highly invasive tumor,frequently disposed in essential areas of the brain,which makes its surgical excision extremely difficult;meanwhile adjuvant therapy remains quite ineffective.Methods:In the current report,a new therapeutic approach in curing malignant neoplasms has been performed on the U87 human glioblastoma model.This approach,termed"Karanahan",is aimed at the eradication of cancer stem cells(CSCs),which were recently shown to be capable of internalizing fragments of extracellular double-stranded DNA.After being internalized,these fragments interfere in the process of repairing interstrand cross-links caused by exposure to appropriate cytostatics,and such an interference results either in elimination of CSCs or in the loss of their tumorigenic potency.Implementation of the approach requires a scheduled administration of cytostatic and complex composite double-stranded DNA preparation.Results:U87 cells treated in vitro in accordance with the Karanahan approach completely lost their tumorigenicity and produced no grafts upon intracerebral transplantation into immunodeficient mice.In SCID mice with developed subcutaneous grafts,the treatment resulted in reliable slowing down of tumor growth rate(P<0.05).In the experiment with intracerebral transplantation of U87 cells followed by surgical excision of the developed graft and subsequent therapeutic treatment,the Karanahan approach was shown to reliably slow down the tumor growth rate and increase the median survival of the mice twofold relative to the control.Conclusions:The effectiveness of the Karanahan approach has been demonstrated both in vitro and in vivo in treating developed subcutaneous grafts as well as orthotopic grafts after surgical excision of the tumor.展开更多
文摘The liver is a unique parenchymal organ with a regenerative capacity allowing it to restore up to 70%of its volume.Although knowledge of this phenomenon dates back to Greek mythology(the story of Prometheus),many aspects of liver regeneration are still not understood.A variety of different factors,including inflammatory cytokines,growth factors,and bile acids,promote liver regeneration and control the final size of the organ during typical regeneration,which is performed by mature hepatocytes,and during alternative regeneration,which is performed by recently identified resident stem cells called“hepatic progenitor cells”.Hepatic progenitor cells drive liver regeneration when hepatocytes are unable to restore the liver mass,such as in cases of chronic injury or excessive acute injury.In liver maintenance,the body mass ratio is essential for homeostasis because the liver has numerous functions;therefore,a greater understanding of this process will lead to better control of liver injuries,improved transplantation of small grafts and the discovery of new methods for the treatment of liver diseases.The current review sheds light on the key molecular pathways and cells involved in typical and progenitor-dependent liver mass regeneration after various acute or chronic injuries.Subsequent studies and a better understanding of liver regeneration will lead to the development of new therapeutic methods for liver diseases.
基金supported by the Russian Ministry of Science and High Education,State Budgeted Project 0259-2021-0013 for the Institute of Cytology and Genetics,Novosibirskthe Russian Foundation for Basic Research(Grant No.18-34-20016)+1 种基金Microscopic examination of bone marrow cells was supported by the Russian Ministry of Science and High EducationState Budgeted Project 0246-2021-0017 for the Institute of Molecular and Cellular Biology,Novosibirsk。
文摘Objective:Glioma is a highly invasive tumor,frequently disposed in essential areas of the brain,which makes its surgical excision extremely difficult;meanwhile adjuvant therapy remains quite ineffective.Methods:In the current report,a new therapeutic approach in curing malignant neoplasms has been performed on the U87 human glioblastoma model.This approach,termed"Karanahan",is aimed at the eradication of cancer stem cells(CSCs),which were recently shown to be capable of internalizing fragments of extracellular double-stranded DNA.After being internalized,these fragments interfere in the process of repairing interstrand cross-links caused by exposure to appropriate cytostatics,and such an interference results either in elimination of CSCs or in the loss of their tumorigenic potency.Implementation of the approach requires a scheduled administration of cytostatic and complex composite double-stranded DNA preparation.Results:U87 cells treated in vitro in accordance with the Karanahan approach completely lost their tumorigenicity and produced no grafts upon intracerebral transplantation into immunodeficient mice.In SCID mice with developed subcutaneous grafts,the treatment resulted in reliable slowing down of tumor growth rate(P<0.05).In the experiment with intracerebral transplantation of U87 cells followed by surgical excision of the developed graft and subsequent therapeutic treatment,the Karanahan approach was shown to reliably slow down the tumor growth rate and increase the median survival of the mice twofold relative to the control.Conclusions:The effectiveness of the Karanahan approach has been demonstrated both in vitro and in vivo in treating developed subcutaneous grafts as well as orthotopic grafts after surgical excision of the tumor.