1.Mechanisms of miR-503 inhibiting radio-resistance of esophageal squamous cell carcinoma cells by targeting ERCC1
KONG Lei ; WANG Junjie ; WANG Jidong ; YU Yonghua ; ZHANG Yingdong ; CUI Di ; ZHANG Yong ; FU Zhixue
Chinese Journal of Cancer Biotherapy 2019;26(9):969-975
Objective: To investigate the mechanism of miR-503 modulates radio-resistance of esophageal squamous cell carcinoma (ESCC) by targeting excision-repair cross-complementing 1 (ERCC1). Methods: The expression level of miR-503 in radio-resistant ESCC tumor tissues and KYSE140 and KYSE140R cells was detected by qPCR. The miR-503 mimic, miR-503 inhibitor or si-ERCC1 was transfected into KYSE140 and KYSE140R cells.After radiation treatment, the colony formation assay and CCK-8 assay were used to detect the proliferation of KYSE140R cells. Flow cytometry was used to detect apoptosis of KYSE140R cells. WB was used to detect changes in protein expression of ERCC1. Dual luciferase reporter gene assay was used to validate the targeting relationship between miR-503 and ERCC1. Results: The expression level of miR-503 was down-regulated in radio-resistant tissues and ESCC cell lines (all P<0.01). Over-expression of miR-503 significantly inhibited cell proliferation and promoted apoptosis of KYSE140R cells (all P<0.01). Dual-luciferase reporter assay validated that ERCC1 was a target gene of miR-503, and miR-503 negatively regulated the expression of ERCC1. Over-expression of miR-503 significantly down-regulated the expression of ERCC1 in KYSE140 and KYSE140R cells (both P<0.01), inhibited cell proliferation (both P<0.01), but significantly increased apoptosis rate (all P<0.01); knockdown of ERCC1 exhibited a similar effect, while knockdown of both ERCC1 and miR-503 reversed the above effects. Conclusion: Over-expression of miR-503 up-regulated the radio-sensitivity of KYSE140R cells by targeting ERCC1.
2.IMRT combined with Iressa for patients with locally advanced non-small cell lung cancer unsuitable for surgery or concurrent chemoradiotherapy:the preliminary results of a phase Ⅱ clinical trial
Zhixue FU ; Xu YANG ; Wenqing WANG ; Lei DENG ; Tao ZHANG ; Nan BI ; Xiaozhen WANG ; Dongfu CHEN ; Zongmei ZHOU ; Luhua WANG ; Jun LIANG
Chinese Journal of Radiation Oncology 2018;27(6):559-563
Objective To observe the objective response rate, survival and safety of radiotherapy combined with Iressa for patients with locally advanced non-small cell lung cancer ( NSCLC) unsuitable for surgery or concurrent chemoradiotherapy. Methods The patients with locally advanced NSCLC unsuitable for surgery or concurrent chemoradiotherapy were recruited and received thoracic intensity-modulated radiotherapy ( IMRT) combined with Iressa 250 mg daily. Results A total of 30 patients were enrolled between July 2014 and March 2017. Twenty-nine patients were analyzed. At 1 month after radiotherapy,the complete response (CR) was 0,partial response (PR) was 21(72%),stable disease (SD) was 6(21%), progressive disease (PD) was 2(7%),the disease control rate (CR+PR+SD) was 93%,and the objective response rate was 72%. The median follow-up time was 25 months. Fourteen ( 48%) patients died,and 15 (52%) survived. Twenty-three (79%) patients obtained PD including local progression in 18(62%) and distant metastasis in 14(48%). The median survival time (MST) was 26 months and the median PFS was 11 months. The 1-year OS and PFS were 79% and 44%,and the 2-year OS and PFS were 55% and 18%. Univariate analysis demonstrated that smoking history and disease stage were influencing factors for OS ( P=0. 035,0. 031) . Moreover, disease stage, the primary tumor diameter, the volume of GTV and PTV were influencing factors for PFS (P=0. 000,0. 016,0. 039,0. 030). Multivariable analysis revealed that disease stage and the volume of PTV were independent prognostic factors for PFS (P=0. 000,0. 012).Two patients ( 7%) developed grade 3 acute adverse events and 7 ( 24%) experienced grade 2 acute irradiation pneumonitis. Conclusions For patients with locally advanced NSCLC unsuitable for surgery or concurrent chemoradiotherapy,IMRT combined with Iressa yields high objective response rate and well tolerance. The long-term clinical efficacy remains to be validated.