Background:Osteosarcoma is the most common bone malignancy in children and adolescents,and 20%-30%of the patients suffer from poor prognosis because of individual chemoresistance.The Hippo/yes-associated protein(YAP) ...Background:Osteosarcoma is the most common bone malignancy in children and adolescents,and 20%-30%of the patients suffer from poor prognosis because of individual chemoresistance.The Hippo/yes-associated protein(YAP) signaling pathway has been shown to play a role in tumor chemoresistance,but no previous report has focused on its involvement in osteosarcoma chemoresistance.This study aimed to investigate the role of the Hippo/YAP signaling pathway in osteosarcoma chemoresistance and to determine potential treatment targets.Methods:Using the Cell Titer-Glo Luminescent cell viability assay and flow cytometry analysis,we determined the proliferation and chemosensitivity of YAP-overexpressing and YAP-knockdown osteosarcoma cells.In addition,using western blotting and the real-time polymerase chain reaction technique,we investigated the alteration of the Hippo/YAP signaling pathway in osteosarcoma cells treated with chemotherapeutic agents.Results:Mammalian sterile 20-like kinase 1(MST1) degradation was increased,and large tumor suppressor kinase1/2(LAT51/2) total protein levels were decreased by methotrexate and doxorubicin,which increased activation and nuclear translocation of YAP.Moreover,YAP increased the proliferation and chemoresistance of MG63 cells.Conclusions:The Hippo/YAP signaling pathway plays a role in osteosarcoma chemoresistance,and YAP is a potential target for reducing chemoresistance.展开更多
Objective:To investigate thyroid-stimulating hormone(TSH)levels and thyroid peroxidase antibody(TPOAb)in early pregnancy and to estimate the risk of development of gestational diabetes mellitus(GDM).Methods:The levels...Objective:To investigate thyroid-stimulating hormone(TSH)levels and thyroid peroxidase antibody(TPOAb)in early pregnancy and to estimate the risk of development of gestational diabetes mellitus(GDM).Methods:The levels of TSH,free thyroxine,free triiodothyronine,and TPOAb were retrospectively evaluated in 2333 pregnant women.All women recruited were divided into groups of TSH high(H),TSH low(L),TSH(H)TPOAb positive(+),TSH(H)TPOAb negative(-),TSH normal(N)TPOAb(+),TSH(L)TPOAb(+),TSH(L)TPOAb(-),and estimated the risk of GDM.Results:TSH level(X^(2)=13.0024,P=0.0015)and TSH combined TPOAb(X^(2)=20.0038,P=0.0012)were correlated to development of GDM.The level of TSH in 95 women was increased,and in 216 women were decreased.Of the 2333 pregnant women,546 patients were diagnosed with GDM,with a prevalence of 23.40%.The prevalence of GDM was 35.78%and 28.70%for the TSH high(H)and TSH low(L)pregnant women,respectively.The increased TSH(P=0.0013,odds ratio:2.09,confidence interval:1.34-3.28)was correlated to increase GDM incidence.TSH(H)TPOAb(+)(n=29),TSH(H)TPOAb(-)(n=58),TSH normal(N)TPOAb(+)(n=265),TSH(L)TPOAb(+)(n=30),TSH(L)TPOAb(-)(n=154)were in this study.The prevalence of GDM was 51.72%,29.31%,23.02%,26.67%,and 29.87%for the TSH(H)TPOAb(+),TSH(H)TPOAb(-),TSH(N)TPOAb(+),TSH(L)TPOAb(+),and TSH(L)TPOAb(-)pregnant women,respectively.Only the TSH(H)TPOAb(+)pregnant women had a significant higher incidence of GDM(P=0.0018,odds ratio:3.63,confidence interval:1.62-8.16).Trimester specific results showed that only second trimester had higher GDM risk either analyze TSH or the combination of TSH and TPOAb.Conclusion:Elevated TSH level and TPOAb positive in the second trimester of pregnancy were correlated to an increased risk of GDM.展开更多
基金supported by the National Natural Science Foundation of China(No.81172553 and 81472513 to WB)
文摘Background:Osteosarcoma is the most common bone malignancy in children and adolescents,and 20%-30%of the patients suffer from poor prognosis because of individual chemoresistance.The Hippo/yes-associated protein(YAP) signaling pathway has been shown to play a role in tumor chemoresistance,but no previous report has focused on its involvement in osteosarcoma chemoresistance.This study aimed to investigate the role of the Hippo/YAP signaling pathway in osteosarcoma chemoresistance and to determine potential treatment targets.Methods:Using the Cell Titer-Glo Luminescent cell viability assay and flow cytometry analysis,we determined the proliferation and chemosensitivity of YAP-overexpressing and YAP-knockdown osteosarcoma cells.In addition,using western blotting and the real-time polymerase chain reaction technique,we investigated the alteration of the Hippo/YAP signaling pathway in osteosarcoma cells treated with chemotherapeutic agents.Results:Mammalian sterile 20-like kinase 1(MST1) degradation was increased,and large tumor suppressor kinase1/2(LAT51/2) total protein levels were decreased by methotrexate and doxorubicin,which increased activation and nuclear translocation of YAP.Moreover,YAP increased the proliferation and chemoresistance of MG63 cells.Conclusions:The Hippo/YAP signaling pathway plays a role in osteosarcoma chemoresistance,and YAP is a potential target for reducing chemoresistance.
文摘Objective:To investigate thyroid-stimulating hormone(TSH)levels and thyroid peroxidase antibody(TPOAb)in early pregnancy and to estimate the risk of development of gestational diabetes mellitus(GDM).Methods:The levels of TSH,free thyroxine,free triiodothyronine,and TPOAb were retrospectively evaluated in 2333 pregnant women.All women recruited were divided into groups of TSH high(H),TSH low(L),TSH(H)TPOAb positive(+),TSH(H)TPOAb negative(-),TSH normal(N)TPOAb(+),TSH(L)TPOAb(+),TSH(L)TPOAb(-),and estimated the risk of GDM.Results:TSH level(X^(2)=13.0024,P=0.0015)and TSH combined TPOAb(X^(2)=20.0038,P=0.0012)were correlated to development of GDM.The level of TSH in 95 women was increased,and in 216 women were decreased.Of the 2333 pregnant women,546 patients were diagnosed with GDM,with a prevalence of 23.40%.The prevalence of GDM was 35.78%and 28.70%for the TSH high(H)and TSH low(L)pregnant women,respectively.The increased TSH(P=0.0013,odds ratio:2.09,confidence interval:1.34-3.28)was correlated to increase GDM incidence.TSH(H)TPOAb(+)(n=29),TSH(H)TPOAb(-)(n=58),TSH normal(N)TPOAb(+)(n=265),TSH(L)TPOAb(+)(n=30),TSH(L)TPOAb(-)(n=154)were in this study.The prevalence of GDM was 51.72%,29.31%,23.02%,26.67%,and 29.87%for the TSH(H)TPOAb(+),TSH(H)TPOAb(-),TSH(N)TPOAb(+),TSH(L)TPOAb(+),and TSH(L)TPOAb(-)pregnant women,respectively.Only the TSH(H)TPOAb(+)pregnant women had a significant higher incidence of GDM(P=0.0018,odds ratio:3.63,confidence interval:1.62-8.16).Trimester specific results showed that only second trimester had higher GDM risk either analyze TSH or the combination of TSH and TPOAb.Conclusion:Elevated TSH level and TPOAb positive in the second trimester of pregnancy were correlated to an increased risk of GDM.