Drug-induced gingival overgrowth(DIGO) is recognized as a side effect of nifedipine(NIF);however, the underlying molecular mechanisms remain unknown. In this study, we found that overexpressed mi R-4651 inhibits cell ...Drug-induced gingival overgrowth(DIGO) is recognized as a side effect of nifedipine(NIF);however, the underlying molecular mechanisms remain unknown. In this study, we found that overexpressed mi R-4651 inhibits cell proliferation and induces G0/G1-phase arrest in gingival mesenchymal stem cells(GMSCs) with or without NIF treatment. Furthermore, sequential window acquisition of all theoretical mass spectra(SWATH-MS) analysis, bioinformatics analysis, and dual-luciferase report assay results confirmed that high-mobility group AT-hook 2(HMGA2) is the downstream target gene of mi R-4651. Overexpression of HMGA2 enhanced GMSC proliferation and accelerated the cell cycle with or without NIF treatment. The present study demonstrates that mi R-4651 inhibits the proliferation of GMSCs and arrests the cell cycle at the G0/G1 phase by upregulating cyclin D and CDK2 while downregulating cyclin E through inhibition of HMGA2 under NIF stimulation. These findings reveal a novel mechanism regulating DIGO progression and suggest the potential of mi R-4651 and HMGA2 as therapeutic targets.展开更多
In recent years, immunotherapy has been gradually established as the fourth frequently adopted antitumor therapy, following surgery, chemotherapy and radiotherapy, for advanced urologic malignancies with an improved u...In recent years, immunotherapy has been gradually established as the fourth frequently adopted antitumor therapy, following surgery, chemotherapy and radiotherapy, for advanced urologic malignancies with an improved understanding of theoretical basis, such as molecular biology and immunology. Thereinto, adoptive cellular immunotherapy （ACI） has become one of the hotspots, which comprises a variety of treatment approaches, such as TIL, CIK cell, ~＇~ T cell, CAR-engineered T cell and Allogeneie stem cell transplantation （alloSCT）. Although preclinical efficacy has been demonstrated remarkably, clinical trials could not consistently show the benefit due to multi-factors in complex immnnosuppressive microenvironment in vivo compared to that of in vitro. Here we review some timely aspects of ACI for advanced urologic malignancies, and describe the current status and limitation of immunotherapy from the cellular level. It＇s our expectation to provide prompting consideration of novel combinatorial ACI strategies and a resurgence of interest in ACI for advanced urologic malignancies.展开更多
基金supported by grants from the National Natural Science Foundation of China(81625005 to Z.P.F.)the Program for“Hundred-Thousand-Ten thousand”Talents in Beijing(2018A16 to Z.P.F.)。
文摘Drug-induced gingival overgrowth(DIGO) is recognized as a side effect of nifedipine(NIF);however, the underlying molecular mechanisms remain unknown. In this study, we found that overexpressed mi R-4651 inhibits cell proliferation and induces G0/G1-phase arrest in gingival mesenchymal stem cells(GMSCs) with or without NIF treatment. Furthermore, sequential window acquisition of all theoretical mass spectra(SWATH-MS) analysis, bioinformatics analysis, and dual-luciferase report assay results confirmed that high-mobility group AT-hook 2(HMGA2) is the downstream target gene of mi R-4651. Overexpression of HMGA2 enhanced GMSC proliferation and accelerated the cell cycle with or without NIF treatment. The present study demonstrates that mi R-4651 inhibits the proliferation of GMSCs and arrests the cell cycle at the G0/G1 phase by upregulating cyclin D and CDK2 while downregulating cyclin E through inhibition of HMGA2 under NIF stimulation. These findings reveal a novel mechanism regulating DIGO progression and suggest the potential of mi R-4651 and HMGA2 as therapeutic targets.
基金supported by a grant from National Natural Science Foundation of China(No.30901481,81372752,81472411)Wu-Jie Ping Medical Foundation(320.6750.13261)
文摘In recent years, immunotherapy has been gradually established as the fourth frequently adopted antitumor therapy, following surgery, chemotherapy and radiotherapy, for advanced urologic malignancies with an improved understanding of theoretical basis, such as molecular biology and immunology. Thereinto, adoptive cellular immunotherapy （ACI） has become one of the hotspots, which comprises a variety of treatment approaches, such as TIL, CIK cell, ~＇~ T cell, CAR-engineered T cell and Allogeneie stem cell transplantation （alloSCT）. Although preclinical efficacy has been demonstrated remarkably, clinical trials could not consistently show the benefit due to multi-factors in complex immnnosuppressive microenvironment in vivo compared to that of in vitro. Here we review some timely aspects of ACI for advanced urologic malignancies, and describe the current status and limitation of immunotherapy from the cellular level. It＇s our expectation to provide prompting consideration of novel combinatorial ACI strategies and a resurgence of interest in ACI for advanced urologic malignancies.
