ABSTRACT
Objective To study the effect and related mechanism of celecoxib on tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL) induced apoptosis of medullary thyroid cancer TT cell line.Methods MTT assay was used to measure the growth inhibition induced by TRAIL and celecoxib alone and their combination.TT cell cycle distribution was analyzed by flowcytometry.Hochest33258 staining and DNA ladder was used to detect the apoptosis of drug combination on TT cells.Western blot was used detect the protein change of cyclin A,Cdk2,caspase-8,c-FLIP,and RIP.Results ①MTT showed the growth inhibition ratio of TT cell intervened by the combination of TRAIL and celecoxib was 47.53％ ± 1.34％,which was much higher than that intervened by TRAIL(7.75 ％ ± 3.84％)and celecoxib alone.The differences had statistical significance (t test,F =5.234,P ＜0.01);②PI detection found the cells' number in G0/G1 phase in celecoxib group and combination group were increased compared to that in control group and TRAIL group(F =242.694,P ＜ 0.01);③Western blot indicated the expression of Cyclin A and Cdk2 were down regulated,there was no statistic significance;④ The apoptosis morph in nuclus was detected by Hochest33258 staining and showed the karyopycnosis and muclear fragmentation were increased in combination group with the apoptosis rate 24.23％ ± 2.91％,which was much higher than that in TRAIL(5.86％ ± 1.41％) and celecoxib(20％ ± 1.24％) (t test,F =1.824,P ＜0.01),the difference has statistic significance;⑤Western blot illustrated the active schizolysis of casplase-8 was higher and the expression of c-FLIP and RIP was down regulated in combination group.Conclusion celecoxib plays a positive effect on TRAIL-reduced apoptosis of medullary thyroid cancer TT cell line,which may due to the cell cycle arrest at G0/G1 phase,down-regulation of c-FLIP and RIP and subsequent activation of caspase-8.
ABSTRACT
Objective To discuss the metastasis principle of cervical lymph nodes in CN0 papillary thyroid carcinoma(PTC) and to define the proper surgery scope.Methods Clinical data of the 450 cases of CN0 PTC patients undergoing surgery from Feb.2008 to Feb.2011 in the First Hospital,Jilin University were retrospectively analyzed.Results There were 219 (48.67％) pN + cases and 231 (51.33 ％) pN0 cases.In CN0 PTC cases,lymph node metastasis was most commonly detected in area Ⅵ,about 46.22％ (208/450) (unilateral cancer 41.08％,bilateral cancer 58.09％).The lymph node metastasis rate was 4.44％ (20/450),6.00％ (27/450),and 8.89％ (40/450)respectively in area IIa,area Ⅲ,and area Ⅳ.The metastasis of lymph node was rare in Vb area,only about 2.22 ％ (10/450).No metastasis was found in the 2 cases undergoing area I lymph node dissection.When the tumor diameter was no less than 1.0 cm,capsule invaded or multifocal,male,＜ 45 years old,lymph node metastasis rate was significantly increased (P ＜ 0.05).In addition,when the tumor was located at the upper pole of the thyroid,the lymph node metastasis rate was 33.57％ (48/143) in Ⅱa,Ⅲ,Ⅳ areas in the affected side.When the tumor was at the lower pole of the thyroid,the lymph node metastasis rate was 10.48％ (13/124)in the contralateral area Ⅵ.Conclusion Lymph node metastasis occurs most commonly in area Ⅵ in PTC,followed by area Ⅱ a,area Ⅲ,area Ⅳ.Routine lymph node dissection in area Ⅵ is recommended for the initial surgery.When the tumor diameter is ≥ 1.0 cm,thyroid capsule invasion is involved or more than 3 metastasized lymph nodes were found in area Ⅵ,the range of lymph node dissection should properly be expanded to area Ⅱa-Ⅳ.When the tumor is located at the lower pole of the thyroid,area Ⅵ in the contralateral side should be cleaned.If the tumor is located at the upper pole of the thyroid,area Ⅱa,Ⅲ,Ⅳ in the affected side should be cleaned.