Background:The role of 1,25-dihydroxyvitamin D3(1,25-(OH)_(2)D_(3))in cancer prevention and treatment is an emerging topic of interest.However,its effects on the stemness of acute myeloid leukemia(AML)cells are poorly...Background:The role of 1,25-dihydroxyvitamin D3(1,25-(OH)_(2)D_(3))in cancer prevention and treatment is an emerging topic of interest.However,its effects on the stemness of acute myeloid leukemia(AML)cells are poorly understood.Methods:The proliferation and differentiation of AML cells(HL60 and NB4)were investigated by the CCK-8 assay,immunocytochemical staining,and flow cytometry.The abilities of HL60 and NB4 cells to form spheres were examined by the cell sphere formation assay.In addition,the levels of stemness-associated markers(SOX2,Nanog,OCT4,and c-Myc)in HL60 and NB4 cells were measured by western blotting and quantitative real-time polymerase chain reaction.Moreover,we obtainedβ-catenin-interacting protein 1(ICAT)-knockout and ICAT-overexpressing HL-60 cells using gene editing and lentiviral infection techniques and investigated the role of ICAT in modulating the stemness-inhibiting effects of 1,25-(OH)_(2)D_(3)using the aforementioned experimental methods.Finally,we validated our findings in vivo using NOD/SCID mice.Results:1,25-(OH)_(2)D_(3)inhibited the proliferation and stemness of AML cells(HL60 and NB4)and induced their differentiation into monocytes.Additionally,the knockdown of ICAT in HL60 cells attenuated the inhibitory effects of 1,25-(OH)_(2)D_(3)on proliferation and stemness and suppressed the expression of stemness markers.Conversely,overexpression of ICAT enhanced the aforementioned inhibitory effects of 1,25-(OH)_(2)D_(3).Consistently,in NOD/SCID mice,1,25-(OH)_(2)D_(3)suppressed tumor formation by HL-60 cells,and the effects of ICAT knockdown or overexpression on 1,25-(OH)_(2)D_(3) aligned with the in vitro findings.Conclusion:1,25-(OH)_(2)D_(3)inhibits AML cell stemness,possibly through modulation of the ICAT-mediated Wnt/β-catenin signaling pathway.展开更多
Cerebrovascular disease is one of the fatal causes of Fabry disease (FD). Brain magnetic resonance imaging findings typically show lacunar infarcts in young patients with FD, but brain hemorrhages in FD are rarely rep...Cerebrovascular disease is one of the fatal causes of Fabry disease (FD). Brain magnetic resonance imaging findings typically show lacunar infarcts in young patients with FD, but brain hemorrhages in FD are rarely reported. We report two cases of FD focusing on cerebral microbleeds (CMBs). Susceptibility-weighted imaging (SWI) and T2*-weighted imaging reveal several lobar and deep CMBs in two patients with no medical history of stroke symptoms, hypertension, and anticoagulant/antiplatelet treatment. SWI can detect a greater number of CMBs than T2*-weighted imaging. Thus, SWI is an excellent tool for identifying underlying CMBs in FD.展开更多
The use of concomitant medications by patients with cancer is observed almost globally;however,little attention has been paid to this topic in the medical literature.Most clinical studies do not describe the type and ...The use of concomitant medications by patients with cancer is observed almost globally;however,little attention has been paid to this topic in the medical literature.Most clinical studies do not describe the type and duration of drugs used at the time of inclusion and during treatment or how these drugs may affect the experimental and/or standard therapy.Even less information has been published on the potential interaction between concomitant medications and tumor biomarkers.However,we do know that concomitant drugs can complicate cancer clinical trials and biomarker development,thus contributing to their interaction,leading to side effects,and resulting in suboptimal adherence to anticancer treatment.On the basis of these premises and moving from the study by Jurisova et al.,which reported the effect of commonly used drugs on the prognosis of women with breast cancer and the detection of circulating tumor cells(CTCs),we comment on the role of CTCs as an emerging diagnostic and prognostic tool for breast cancer.We also report the known and hypothesized mechanisms of CTC interplay with other tumor and blood components,possibly modulated by widespread drugs,including over-the-counter compounds,and discuss the possible implications of commonly used concomitant medications on CTC detection and clearance.After considering all these points,it is conceivable that concomitant drugs are not necessarily a problem,but on the contrary,their virtuous mechanisms can be exploited to reduce tumor spread and enhance the effect of anticancer therapies.展开更多
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2022B1515230007).
文摘Background:The role of 1,25-dihydroxyvitamin D3(1,25-(OH)_(2)D_(3))in cancer prevention and treatment is an emerging topic of interest.However,its effects on the stemness of acute myeloid leukemia(AML)cells are poorly understood.Methods:The proliferation and differentiation of AML cells(HL60 and NB4)were investigated by the CCK-8 assay,immunocytochemical staining,and flow cytometry.The abilities of HL60 and NB4 cells to form spheres were examined by the cell sphere formation assay.In addition,the levels of stemness-associated markers(SOX2,Nanog,OCT4,and c-Myc)in HL60 and NB4 cells were measured by western blotting and quantitative real-time polymerase chain reaction.Moreover,we obtainedβ-catenin-interacting protein 1(ICAT)-knockout and ICAT-overexpressing HL-60 cells using gene editing and lentiviral infection techniques and investigated the role of ICAT in modulating the stemness-inhibiting effects of 1,25-(OH)_(2)D_(3)using the aforementioned experimental methods.Finally,we validated our findings in vivo using NOD/SCID mice.Results:1,25-(OH)_(2)D_(3)inhibited the proliferation and stemness of AML cells(HL60 and NB4)and induced their differentiation into monocytes.Additionally,the knockdown of ICAT in HL60 cells attenuated the inhibitory effects of 1,25-(OH)_(2)D_(3)on proliferation and stemness and suppressed the expression of stemness markers.Conversely,overexpression of ICAT enhanced the aforementioned inhibitory effects of 1,25-(OH)_(2)D_(3).Consistently,in NOD/SCID mice,1,25-(OH)_(2)D_(3)suppressed tumor formation by HL-60 cells,and the effects of ICAT knockdown or overexpression on 1,25-(OH)_(2)D_(3) aligned with the in vitro findings.Conclusion:1,25-(OH)_(2)D_(3)inhibits AML cell stemness,possibly through modulation of the ICAT-mediated Wnt/β-catenin signaling pathway.
文摘Cerebrovascular disease is one of the fatal causes of Fabry disease (FD). Brain magnetic resonance imaging findings typically show lacunar infarcts in young patients with FD, but brain hemorrhages in FD are rarely reported. We report two cases of FD focusing on cerebral microbleeds (CMBs). Susceptibility-weighted imaging (SWI) and T2*-weighted imaging reveal several lobar and deep CMBs in two patients with no medical history of stroke symptoms, hypertension, and anticoagulant/antiplatelet treatment. SWI can detect a greater number of CMBs than T2*-weighted imaging. Thus, SWI is an excellent tool for identifying underlying CMBs in FD.
基金the Fondazione Associazione Italiana Ricerca contro il Cancro(AIRC)Investigator Grant(IG)numbers 20774 and IG 21694,respectively.
文摘The use of concomitant medications by patients with cancer is observed almost globally;however,little attention has been paid to this topic in the medical literature.Most clinical studies do not describe the type and duration of drugs used at the time of inclusion and during treatment or how these drugs may affect the experimental and/or standard therapy.Even less information has been published on the potential interaction between concomitant medications and tumor biomarkers.However,we do know that concomitant drugs can complicate cancer clinical trials and biomarker development,thus contributing to their interaction,leading to side effects,and resulting in suboptimal adherence to anticancer treatment.On the basis of these premises and moving from the study by Jurisova et al.,which reported the effect of commonly used drugs on the prognosis of women with breast cancer and the detection of circulating tumor cells(CTCs),we comment on the role of CTCs as an emerging diagnostic and prognostic tool for breast cancer.We also report the known and hypothesized mechanisms of CTC interplay with other tumor and blood components,possibly modulated by widespread drugs,including over-the-counter compounds,and discuss the possible implications of commonly used concomitant medications on CTC detection and clearance.After considering all these points,it is conceivable that concomitant drugs are not necessarily a problem,but on the contrary,their virtuous mechanisms can be exploited to reduce tumor spread and enhance the effect of anticancer therapies.
