背景与目的:提高晚期非小细胞肺癌患者的生活质量是肿瘤学者关注的问题之一。吉非替尼已广泛用于治疗晚期非小细胞肺癌。本研究探讨吉非替尼对晚期非小细胞肺癌患者生活质量的影响。方法:70例晚期非小细胞肺癌患者,每日口服吉非替尼250...背景与目的:提高晚期非小细胞肺癌患者的生活质量是肿瘤学者关注的问题之一。吉非替尼已广泛用于治疗晚期非小细胞肺癌。本研究探讨吉非替尼对晚期非小细胞肺癌患者生活质量的影响。方法:70例晚期非小细胞肺癌患者,每日口服吉非替尼250mg,直至病情进展或出现严重不良反应。采用欧洲癌症研究和治疗组织(European Organization for Research and Treatment of Cancer,EORTC)简体中文版EORTC QLQ-C30和QLQ-LC13问卷对治疗前、后症状和生活质量的改变进行评价。结果:58例患者(85.3%)完成了问卷调查。治疗前和治疗8周后患者5种功能状态(躯体、角色、情感、认知、社会)的均值分别为52和63,49和56,64和68,60和65,52和61,整体生活质量评分的均值分别为53和60,差异有显著性(P<0.05);治疗前、后全身症状(乏力、食欲不振)的均值分别为61和58,52和48,肺癌相关症状(呼吸困难、咳嗽、咯血、胸痛)的均值分别为55和49,54和47,28和27,29和25,其中乏力、呼吸困难、咳嗽、胸痛的差异有显著性(P<0.05)。治疗后5种功能状态和整体生活质量的有效率均超过50%,全身症状和肺癌相关症状的有效率均超过40%。症状和生活质量的改善与疾病控制相一致。生活质量改善者生存延长。结论:吉非替尼明显改善晚期非小细胞肺癌患者的症状和生活质量。展开更多
Reduced radiosensitivity of lung cancer cells represents a pivotal obstacle in clinical oncol- ogy. The hypoxia-inducible factor （HIF）-lα plays a crucial role in radiosensitivity, but the detailed mechanisms remain...Reduced radiosensitivity of lung cancer cells represents a pivotal obstacle in clinical oncol- ogy. The hypoxia-inducible factor （HIF）-lα plays a crucial role in radiosensitivity, but the detailed mechanisms remain elusive. A relationship has been suggested to exist between hypoxia and autophagy recently. In the current study, we studied the effect of hypoxia-induced autophagy on radioresistance in lung cancer cell lines. A549 and H1299 cells were cultured under normoxia or hypoxia, followed by ir- radiation at dosage ranging from 0 to 8 Gy. Clonogenic assay was performed to calculate surviving frac- tion. EGFP-LC3 plasmid was stably transfected into cells to monitor autopbagic processes. Western blotting was used to evaluate the protein expression levels of HIF-lα, c-Jun, phosphorylated c-Jun, Be- clin 1, LC3 and p62. The mRNA levels of Beclin 1 were detected by qRT-PCR. We found that under hypoxia, both A549 and H1299 cells were radio-resistant compared with normoxia. Hypoxia-induced elevated HIF-1α protein expression preferentially triggered autophagy, accompanied by LC3 induction, EGFP-LC3 puncta and p62 degradation. In the meantime, HIF-1α increased downstream c-Jun phos- phorylation, which in turn upregulated Beclin 1 mRNA and protein expression. The upregulation of Be- clin 1 expression, instead of HIF-1α, could be blocked by SP600125 （a specific inhibitor of c-Jun NH2- terminal kinase）, followed by suppression of autophagy. Under hypoxia, combined treatment of irradia- tion and chloroquine （a potent autophagy inhibitor） significantly decreased the survival potential of lung cancer cells in vitro and in vivo. In conclusion, hypoxia-induced autophagy through evaluating Beclinl expression may be considered as a target to reverse the radioresistance in cancer cells.展开更多
文摘背景与目的:提高晚期非小细胞肺癌患者的生活质量是肿瘤学者关注的问题之一。吉非替尼已广泛用于治疗晚期非小细胞肺癌。本研究探讨吉非替尼对晚期非小细胞肺癌患者生活质量的影响。方法:70例晚期非小细胞肺癌患者,每日口服吉非替尼250mg,直至病情进展或出现严重不良反应。采用欧洲癌症研究和治疗组织(European Organization for Research and Treatment of Cancer,EORTC)简体中文版EORTC QLQ-C30和QLQ-LC13问卷对治疗前、后症状和生活质量的改变进行评价。结果:58例患者(85.3%)完成了问卷调查。治疗前和治疗8周后患者5种功能状态(躯体、角色、情感、认知、社会)的均值分别为52和63,49和56,64和68,60和65,52和61,整体生活质量评分的均值分别为53和60,差异有显著性(P<0.05);治疗前、后全身症状(乏力、食欲不振)的均值分别为61和58,52和48,肺癌相关症状(呼吸困难、咳嗽、咯血、胸痛)的均值分别为55和49,54和47,28和27,29和25,其中乏力、呼吸困难、咳嗽、胸痛的差异有显著性(P<0.05)。治疗后5种功能状态和整体生活质量的有效率均超过50%,全身症状和肺癌相关症状的有效率均超过40%。症状和生活质量的改善与疾病控制相一致。生活质量改善者生存延长。结论:吉非替尼明显改善晚期非小细胞肺癌患者的症状和生活质量。
基金supported by the National Natural Science Foundation of China(No.81201779)
文摘Reduced radiosensitivity of lung cancer cells represents a pivotal obstacle in clinical oncol- ogy. The hypoxia-inducible factor （HIF）-lα plays a crucial role in radiosensitivity, but the detailed mechanisms remain elusive. A relationship has been suggested to exist between hypoxia and autophagy recently. In the current study, we studied the effect of hypoxia-induced autophagy on radioresistance in lung cancer cell lines. A549 and H1299 cells were cultured under normoxia or hypoxia, followed by ir- radiation at dosage ranging from 0 to 8 Gy. Clonogenic assay was performed to calculate surviving frac- tion. EGFP-LC3 plasmid was stably transfected into cells to monitor autopbagic processes. Western blotting was used to evaluate the protein expression levels of HIF-lα, c-Jun, phosphorylated c-Jun, Be- clin 1, LC3 and p62. The mRNA levels of Beclin 1 were detected by qRT-PCR. We found that under hypoxia, both A549 and H1299 cells were radio-resistant compared with normoxia. Hypoxia-induced elevated HIF-1α protein expression preferentially triggered autophagy, accompanied by LC3 induction, EGFP-LC3 puncta and p62 degradation. In the meantime, HIF-1α increased downstream c-Jun phos- phorylation, which in turn upregulated Beclin 1 mRNA and protein expression. The upregulation of Be- clin 1 expression, instead of HIF-1α, could be blocked by SP600125 （a specific inhibitor of c-Jun NH2- terminal kinase）, followed by suppression of autophagy. Under hypoxia, combined treatment of irradia- tion and chloroquine （a potent autophagy inhibitor） significantly decreased the survival potential of lung cancer cells in vitro and in vivo. In conclusion, hypoxia-induced autophagy through evaluating Beclinl expression may be considered as a target to reverse the radioresistance in cancer cells.
