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As the meeting point of signaling pathways actived by growth factors and amino acids,especially leucine,in tumor cells,mammalian target of rapamycin (mTOR) plays an important role as a center factor of regulation.Recently,it was acknowledged gradually that feedback activation mechanisms of mTOR can influence the efficiency of rapamycin and its analogs in antitumor therapy.Thus,the study about feedback mechanism of mTOR and the combination therapy of mTOR inhibitors and specificd pathway inhibitors has become the hot area in cancer therapy and prevention.
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Objective To detect the apoptosis of femoral head cartilage cells and to observe the expression of apoptosis-related proteins in the tissues of the femoral head,as well as to explore the main pathway for regulating the apoptosis in steroid induced by juvenile rabbit models with avascular necrosis of femoral head.Methods The models with avascular necrosis of the femoral head and the control group model were made in New Zealand infancy albino rabbits induced by glucocorticoid(GC).The immunohistochemical method was used to detect the expressions of Caspase3,Caspase-8,apoptosis protease activating factor-1 (apaf-1),calpain-1 in the femoral heads.Results 1.The integrated optical density(IOD) values of Caspase-3 in GC-induced subgroup,the subgroup that was not induced by GC and control group were 25 142.72 ± 21 528.48,2 069.63 ± 1 096.96 and 301.80 ± 99.66,respectively.The IOD values of Caspase-8 in GC-induced subgroup,the subgroup respectively and the control group were 24 942.63 ± 18 942.99,2 016.31 ± 1 518.70,236.85 ±97.94,respectively.The IOD values of apaf-1 in GC-induced subgroup,the subgroup that was not induced by GC and the control group were 8 5 14.23 ± 6 384.20,1 118.49 ± 1 360.59,95.13 ± 38.05,respectively.The IOD values of calpain-1 in GC-induccd subgroup,the subgroup that was not induced by GC and control group were 9 636.71 ± 9 123.81,1 881.10 ± 3 277.86,126.71 ± 47.35,respectively.The IOD value differences of the Caspase-3 between GC-induced subgroup and the subgroup that was not induced by GC,the control group were extremely significant (H =l 1.470,23.996,P ＜ 0.01).The IOD value differences of the Caspase-8,apaf-1,calpain-1 between GC-induced subgroup and the control group were extremely significant (H =22.178,22.808,13.553,P ＜ 0.01).2.The linear regression analysis results showed that under the joint action of Caspase-8,apaf-1,calpain-1,only the Caspase-8 could significantly predict Caspase-3,and its regression equation regression got significant effect and could explain 40.3％ of the variance;while the regression effects of the apaf-1 and calpain-1 to Caspase-3 were not significant.Conclusion Death receptor pathway might play a major regulation role in the apoptotic process of avascular necrosis.