ABSTRACT
Objective:To explore the impacts of postoperative radiotherapy on long-term survival of the patients with resectable locally advanced (T 3-4and/or N +) biliary tract cancers (BTCs) and to analyze the prognostic factors. Methods:The patients with locally advanced gallbladder cancer ( n=1 922) and the patients with extrahepatic biliary duct cancer ( n=3 408) who received surgical resection during 2006-2016 were selected from the Surveillance, Epidemiology, and End Result (SEER) database. They were grouped according to different treatment schemes (only surgery and surgery + radiation). The propensity score matching (PSM) method was employed to adjust the differences in baseline prognostic characteristics between patients who received only surgery and those treated with surgery+ radiation. The role of the two treatment schemes on the survival of the patients was analyzed using the Kaplan-Meier method and the prognosis factors were assessed using the Cox regression. Results:The 1 174 patients with gallbladder cancers and the 2 144 patients with extrahepatic biliary duct cancer were respectively matched according to propensity scores. The postoperative radiotherapy showed a significant advantage in 5-year cancer-specific survival (CSS) compared to only surgery for both the patients with gallbladder cancer ( χ2=35.73, P< 0.001) and those with extrahepatic biliary duct cancer ( χ2=9.878, P=0.002). After adjusting related covariates, independent prognostic factors for all the patients included pathological grading, T status, N status, treatment pattern, and age. For the patients with extrahepatic biliary duct cancer, independent prognostic factors also included race and year of diagnosis. The benefits of postoperative radiotherapy were observed in various clinicopathologic characteristics except for the patients with T 1-2 gallbladder cancer and the extrahepatic biliary duct cancer patients with a pathological grade of Ⅰ-Ⅱ and N 0 status or with age ≥ 70. Conclusions:Long-term survival benefits can be gained through postoperative radiotherapy for the patients with resectable locally advanced (T 3-4 and/or N+ ) BTCs. However, adjuvant radiation should be cautiously adopted for the patients with T 1-2 gallbladder cancer and the extrahepatic biliary duct cancer patients with a pathological grade of I-Ⅱ and N 0 status or with age ≥70.
ABSTRACT
Objective:To investigate the role of NIMA-related kinase-7 (NEK7) in breast cancer (BC) and its potential molecular mechanism.Methods:Quantitative real-time reverse-transcription (RT-qPCR) was used to detect the expression of NEK7 in BC tissue and cell lines. The effect of NEK7 on BC cell proliferation was examined by CCK-8. Proteins interacted with NEK7 were screened in Biological database. The effect of overexpression of NOD-like receptor protein 3 (NLRP3) on BC cell proliferation was evaluated. Western blot was used to detect NLRP3 protein expression, and ELISA was employed to evaluate IL-1β and IL-18 expression level.Result:NEK7 was upregulated in BC tissues and cells, and enforced-expression of NEK7 promoted BC cell proliferation[NEK7 over-expression group: 24 h: (0.33±0.02) , 48 h: (0.59±0.02) , 72 h: (0.76±0.02) ; Blank group: 24 h: (0.30±0.02) , 48 h: (0.45±0.02) , 72 h: (0.62±0.03) ; NEK7 empty vector group: 24 h: (0.32±0.02) , 48 h: (0.46±0.02) , 72 h: (0.63±0.03) ]. There was a positive correlation between NEK7 and NLRP3 ( R=0.13) . Overexpression of NLRP3 increased the proliferation ability of BC cell[NLRP3 over-expression group: 24 h: (0.35±0.02) , 48 h: (0.65±0.02) , 72 h: (0.80±0.03) ; Blank group: 24 h: (0.33±0.02) , 48 h: (0.51±0.02) , 72 h: (0.66±0.03) ; NLRP3 empty vector group: 24 h: (0.34±0.02) , 48 h: (0.52±0.03) , 72 h: (0.66±0.03) ]. NEK7 could positively regulate NLRP3 protein and up-regulate IL-1β (NEK7 over-expression group: 129.96±7.62 pg/ml, Blank group: 19.80±2.42pg/ml, NEK7 empty vector group: 21.30±1.77 pg/ml) and IL-18 (NEK7 over-expression group: 144.08±17.20 pg/ml, Blank group: 16.84±2.34pg/ml, NEK7 empty vector group: 17.64±1.94 pg/ml) expression. Conclusion:The upregulation of NEK7 was involved in the process of BC progression by inducing NLRP3 inflammasome activation, suggesting that NEK7 might be a promising therapeutic target for BC.
ABSTRACT
Objective To assess the outcomes of involved field irradiation (IFI) and elective nodal irradiation (ENI) in patients older than 70 years with esophageal squamous-cell carcinoma(SCC) receiving radical IMRT,and to determine whether IFI is feasible in these patients.Methods Totally 79 patients older than 70 years diagnosed with SCC of esophagus without distant metastases were collected.48 patients were received IFI,and the other 31 patients were treated with ENI.With a median follow-up time of 24 months,disease-free survival,overall survival,patterns of failure,irradiated lung dose and radiation pneumonitis were observed and compared between IFI and ENI groups.Results In IFI and ENI arm,the disease-free survival rates of 1,2,3 years were 60.4％,34.9％,29.7％ and 64.5％,54.0％,35.0％,respectively(P ＞0.05).The 1-,2-,and 3-year survival rates were 72.9％,43.4％,31.5％ for the IFI arm,and 73.0％,53.0％,38.3％ for the ENI arm(P ＞ 0.05).The ENI arm had a tendency to expand survival,but the two arms had no significant difference (P ＞ 0.05).The patterns of failure also had no difference between the two arms.Distant failure,local failure,uninvolved nodal failure in IFI arm were 22.9％,27.0％,4.2％,while in ENI arm were 25.8％,0,19.4％,all of them had no significant difference (P ＞ 0.05).However,the lung V5,V20,mean lung dose in ENI arm were higher than that in IFI and all of them had a significantly difference (t =4.66,29.90,15.63,P ＜ 0.05).The radiation pneumonitis rates were higher in ENI than in IFI arm.The rates of degree 1-2 and degree 3 were 22％,19％,and 13％ and 4％ in the two arms,respectively,with a significantly difference(x2 =4.55,4.77,P ＜ 0.05).Conclusions It is feasible that IFI for definitive IMRT in the elderly patients older than 70 years with SCC,because it got similar disease-free survival and overall survival but with less lung doses along with decreased radio-pulmonary lesion when compared with ENI.