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Prevalence and clinical significance of pathogenic germline BRCA1/2 mutations in Chinese non-small cell lung cancer patients

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Cancer Biology & Medicine 2019年第3期16卷 556-564页

作者： Xingsheng Hu Dongyong Yang Yalun Li Li Li Yan Wang Peng Chen Song Xu Xingxiang Pu Wei Zhu Pengbo Deng Junyi Ye Hanhan Zhang Analyn Lizaso Hao Liu Xinru Mao Hai Huang Qian Chu Chengping Hu Department of Medical Oncology Cancer HospitalChinese Academy of Medical SciencesBeijing100021China Department of Pulmonary Medicine Second Affiliated Hospital of Fujian Medical UniversityQuanzhou362100China Department of Respiratory Medicine West China HospitalSichuan UniversityChengdu610041China Department ofRespiratory Medicine Daping HospitalChongqing400042China Department of Respiratory Medicine Xinqiao HospitalArmy Medical UniversityChongqing400037China Department of Medical Oncology Tianjin Medical University CancerInstitute and HospitalNational Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Tianjin's Clinical Research Center for Cancer Tianjin300060China Department of Thoracic Oncology TianjinMedical University General HospitalTianjin300052China Department of Medical Oncology Hunan Cancer HospitalChangsha410006China Department of Pathology Xiangya HospitalCentral South UniversityChangsha410008China Department of Respiratory Medicine Xiangya HospitalCentral South UniversityChangsha410008China Burning RockBiotech Guangzhou510300China Department of Oncology Tongji Hospital of Tongji Medical CollegeHuazhongUniversity of Science and TechnologyWuhan430022China

Objective: Germline alterations in the breast cancer susceptibility genes type 1 and 2, BRCA1 and BRCA2, predispose individuals to hereditary cancers, including breast, ovarian, prostate, pancreatic, and stomach *** evidence suggests inherited genetic susceptibility to lung *** present study aimed to survey the prevalence of pathogenic germline BRCA mutations(gBRCAm) and explore the potential association between gBRCAm and disease onset in Chinese advanced non-small cell lung cancer(NSCLC) ***: A total of 6,220 NSCLC patients were screened using capture-based ultra-deep targeted sequencing to identify patients harboring germline BRCA1/2 ***: Out of the 6,220 patients screened, 1.03%(64/6,220) of the patients harbored the pathogenic gB RCAm, with BRCA2 mutations being the most predominant mutations(49/64, 76.5%).Patients who developed NSCLC before 50 years of age were more likely to carry gBRCAm(P = 0.036).Among the patients harboring classic lung cancer driver mutations, those with concurrent gBRCAm were significantly younger than those harboring the wild-type gBRCA(P = 0.029).By contrast, the age of patients with or without concurrent gBRCAm was comparable to those of patients without the driver mutations(P = 0.972).In addition, we identified EGFR-mutant patients with concurrent gBRCAm who showed comparable progression-free survival but significantly longer overall survival(P = 0.002) compared to EGFR-mutant patients with wild-type germline ***: Overall, our study is the largest survey of the prevalence of pathogenic gBRCAm in advanced Chinese NSCLC *** suggested a lack of association between germline BRCA status and treatment outcome of *** addition,results showed a positive correlation between pathogenic gB RCAm and an early onset of NSCLC.

关键词： Germline BRCA mutations non-small cell lung cancer prevalence BRCA1 BRCA2

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Pre-irradiation with low-dose ^(12)C^(6+) beam significantly enhances the efficacy of AdCMV-p53 gene therapy in human non-small lung cancer

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Science China(Physics,Mechanics & Astronomy) 2007年第2期50卷 221-230页

作者： LIU Bing1,2,ZHANG Hong1,LI WenJian1,LI Qiang1,ZHOU GuangMing1,XIE Yi1,2,HAO JiFang1,MIN FengLing1,2,ZHOU QingMing1,2 & DUAN Xin1,21 Institute of Modern Physics,Chinese Academy of Sciences,Lanzhou 730000,China 2 Graduate University of Chinese Academy of Sciences,Beijing 100039,China Institute of Modern Physics Chinese Academy of Sciences Lanzhou China Graduate University of Chinese Academy of Sciences Beijing China

The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOI of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in 12C6+ beam induced AdCMV-p53 infected cells were more than 90%, which were signifi-cantly more than those in γ-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6+ beam significantly prevented the G0/G1 arrest and activated G2/M checkpoints. The pre-exposure to 12C6+ beam significantly improved cell to apoptosis. RBEs for the 12C6+ + AdCMV-p53 infection groups were 30%-60%, 20%-130% and 30%-70% more than those for the 12C6+-irradiated only, AdCMV-p53 infected only, and γ-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose 12C6+ beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.

关键词： heavy-ion beam gene therapy p53 non-small lung cancer adenoviral vector low dose

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Radiofrequency deep hyperthermia combined with chemotherapy in the treatment of advanced non-small cell lung cancer

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Chinese Medical Journal 2019年第8期132卷 922-927页

作者： Wen-Hui Yang Jun Xie Zhi-Yong Lai Mu-Dan Yang Ge-Hong Zhang Yuan Li Jian-Bing Mu Jun Xu Department of Biochemistry and Molecular Biology Shanxi Medical UniversityTaiyuanShanxi 030001China Shanxi Academy of Medical Sciences Shanxi Dayi HospitalTaiyuanShanxi 030032China Shanxi Province Cancer Hospital Affiliated Cancer Hospital of Shanxi Medical UniversityTaiyuanShanxi 030013China The First Hospital of Shanxi Medical University TaiyuanShanxi 030001China Department of Thoracic Surgery National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Laboratory of Malaria and Vector Research National Institute of Allergy and Infectious DiseasesNational Institutes of HealthRockvilleMD 20852USA

Background:In the era of precision medicine,chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene *** to reduce the toxicity and increase the efficiency of chemotherapy is worth *** study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy(HCT)for advanced patients with non-small cell lung cancer(NSCLC),especially those with malignant pleural ***:We retrospectively evaluated medical records of 93 patients with advanced NSCLC(stage IIIB-IV)from March 2011 to January *** patients were divided into HCT and chemotherapy(CT)*** HCT group was treated with gemcitabine and cisplatin(GP)regimen combined with regional radiofrequency deep hyperthermia,while the CT group was treated with GP regimen *** with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or *** treatment results and adverse reactions were compared and analyzed after *** 19.0 software(SPSS Inc.,USA)was used for statistical data processing.P values less than 0.05 were accepted to be statistically ***:Among the 93 patients,HCT group included 48 patients(16 patients with malignant pleural effusion),CT group included 45 patients(10 patients with malignant pleural effusion).There was no significant difference between the two groups in patient *** overall response rate(ORR)of pleural effusions was much better in HCT group than that in CT group(81.2%vs.40.0%,P=0.046).The patients in HCT group had lower incidence rate of weakness(12.5%us.46.7%,χ^2=13.16,P<0.001)and gastrointestinal(25.0%vs.77.8%,χ^2=25.88,P<0.001)adverse reactions than that in CT *** objective tumor response and survival showed no significant ***:Hyperthermia combined with chemotherapy might lead to the development of better therapeutic strategy for advanced NSC

关键词： Advanced non-small cell lung cancer Chemotherapy Combination therapy Hyperthermia

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The spatiotemporal evolution of EGFR C797S mutation in EGFR-mutant non-small cell lung cancer:opportunities for third-generation EGFR inhibitors re-challenge

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Science Bulletin 2019年第8期64卷 499-503页

作者： Yi-Chen Zhang Qing Zhou Zhi-Hong Chen Ming-Feng Zhang Jin-Ji Yang Hai-Yan Tu Xu-Chao Zhang Chong-Rui Xu Hong-Hong Yan Xiao-Xiao Peng Xiao-Yan Bai Shao-Kun Chuai Jun-Yi Ye Yi-Long Wu The Second School of Clinical Medicine Southern Medical University Guangdong Lung Cancer Institute Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences Burning Rock Biotech

Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated impressive activity in EGFR T790M-positive non-small cell lung cancer (NSCLC) progressed from prior EGFR-TKI... 详细信息

关键词： cis The spatiotemporal evolution of EGFR C797S mutation in EGFR-mutant non-small cell lung cancer:opportunities for third-generation EGFR inhibitors re-challenge

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non-small bowel lesion detection at small bowel capsule endoscopy: A comprehensive literature review

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World Journal of Clinical Cases 2018年第15期6卷 901-907页

作者： Apostolos Koffas Faidon-Marios Laskaratos Owen Epstein Gastroenterology Department University Hospital of Larisa Centre for Gastroenterology Royal Free Hospital

small bowel capsule endoscopy is a minimally-invasive endoscopic investigation that is often used in clinical practice to investigate overt or occult gastrointestinal(GI) bleeding among other clinical indications. International guidance recommends small bowel capsule endoscopy as a first-line investigation to detect abnormalities in the small bowel, when gastroscopy and colonoscopy fail to identify a cause of GI bleeding. It can diagnose with accuracy abnormalities in the small bowel. However, there has been increasing evidence indicating that small bowel capsule endoscopy may also detect lesions outside the small intestine that are within the reach of conventional endoscopy and have been probably missed during prior endoscopic investigations. Such lesions vary from vascular deformities to malignancy and their detection often alters patient management, leading to further endoscopic and/or surgical interventions. The current study attempts to review all available studies in the literature and summarise their relevant findings.

关键词： Obscure gastrointestinal bleeding small bowel capsule endoscopy non-small bowel lesions Overt gastrointestinal bleeding Occult gastrointestinal bleeding Iron deficiency anaemia

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Prognostic model of survival outcomes in non-small cell lung cancer patients initiated on afatinib: pooled analysis of clinical trial data

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Cancer Biology & Medicine 2019年第2期16卷 341-349页

作者： Ashley M. Hopkins Adel Shahnam Sasha Zhang Chris S. Karapetis Andrew Rowland Michael J. Sorich Flinders Centre for Innovation in Cancer Department of Clinical Pharmacology College of Medicine and Public Health Flinders University Adelaide 5042 Australia The Canberra Hospital Garran 2605 Australia

Objective: Several predictors of survival have been identified in EGFR-positive non-small cell lung cancer(NSCLC) patients treated with first generation EGFR inhibitors. Prognostic models of survival outcomes with afatinib have not been ***: A prognostic tool for overall survival(OS)/progression free survival(PFS) based on pre-treatment clinicopathological factors was developed for EGFR-positive advanced NSCLC patients treated with first-line afatinib using penalised regression of individual-participant data from LUX-Lung 3 and 6(n = 468). Favourable, intermediate and poor risk groups were identified and externally validated using LUX-Lung 1(n = 390) and LUX-Lung 2(n = 129) trials that initiated afatinib following previous chemotherapy or EGFR inhibitor ***: Discriminative performance was good in the development and validation cohorts. For patients treated with first-line afatinib, the median OS for the favourable, intermediate and poor risk groups were > 47.7, 29.3 and 16.4 months, respectively, and the median PFS were 17.3, 13.2 and 8.3 months, respectively. The improvement in median OS with afatinib use compared to chemotherapy was > 12.4 months for the favourable risk group, whereas no OS benefit was apparent for the poor risk group. The improvement in median PFS with afatinib use compared to chemotherapy was 10.2 months for the favourable risk group and 3.2 months for the poor risk ***: A prognostic tool was developed and validated to identify favourable, intermediate and poor risk groups for OS/PFS in EGFR-positive advanced NSCLC patients treated with afatinib. The prognostic groups can inform the likely absolute OS/PFS benefit expected from afatinib compared to chemotherapy in first-line treatment.

关键词： Afatinib non-small cell lung cancer prognostic model

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Survival and prognostic factors of non-small cell lung cancer patients with postoperative locoregional recurrence treated with radical radiotherapy

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Chinese Journal of Cancer 2017年第11期36卷 657-664页

作者： Li Ma Bo Qiu Jun Zhang Qi-Wen Li Bin Wang Xu-Hui Zhang Meng-Yun Qiang Zhao-Lin Chen Su-Ping Guo Hui Liu Department of Radiation Oncology Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine 651 Dongfeng Road EastGuangzhou Guangdong 510060 P. R. China

Background: Locoregional recurrence remains the challenge for long-term survival of non-small cell lung cancer(NSCLC) patients after radical surgery, and curative-intent radiotherapy could be a treatment choice. This study aimed to assess the survival and prognostic factors of patients with postoperative locoregionally recurrent NSCLC treated with radical ***: We reviewed medical records of 74 NSCLC patients with postoperative locoregional recurrence who received radical radiotherapy between April 2012 and February 2016 at Sun Yat-sen University Cancer Center(Guangzhou, China). The efficacy and safety of radical radiotherapy were analyzed. The probability of survival was estimated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used to identify prognostic ***: Grade 3/4 adverse events included neutropenia(8 cases, 10.8%), esophagitis(7 cases, 9.5%), pneumonitis(1 case, 1.4%), and vomiting(1 case, 1.4%).The 2-year overall survival, progression-free survival, local recurrencefree survival(LRFS), and distant metastasis-free survival(DMFS) rates of all patients were 84.2,42.5,70.0, and 50.9%,respectively. Univariate and multivariate analyses showed that a higher biological effective dose(BED) of radiation was associated with longer LRFS [hazard ratios(HR)=0.317,95% confidence interval(CI) = 0.112-0.899, P = 0.016] and that wild-type epidermal growth factor receptor(EGFR) was associated with longer DMFS compared with EGFR mutation(HR = 0.383,95% CI=0.171-0.855, P = 0.019).Conclusions: Radical radiotherapy is effective and well-tolerated in NSCLC patients with postoperative locoregional recurrence. High BED is a predictor for long LRFS, and the presence of wild-type EGFR is a predictor for long DMFS.

关键词： non-small cell lung cancer Locoregional recurrence Radical radiotherapy Biological effective dose Epidermal growth factor receptor

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First-line pemetrexed-platinum doublet chemotherapy with or without bevacizumab in non-squamous non-small cell lung cancer: A real-world propensity score-matched study in China

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Chinese Journal of Cancer Research 2019年第5期31卷 749-758页

作者： Fei Qi Xingsheng Hu Yutao Liu Zhijie Wang Jianchun Duan Jie Wang Mei Dong Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

Objective: To evaluate the efficacy and safety profile of first-line bevacizumab(Bev)-containing pemetrexedplatinum chemotherapy in a real-world Chinese cohort with advanced non-squamous non-small cell lung cancer(NS-NSCLC).Methods: A total of 415 eligible patients with NS-NSCLC who received first-line pemetrexed-platinum chemotherapy at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between February 2010 and September 2017 were reviewed retrospectively: 309 Bev(-) and 106 Bev(+) cases. Bev was administered at 7.5 mg/kg every 3 weeks in the Bev(+) group. To reduce the risk of a selection bias, a propensity score-matching(PSM) was conducted and 105 pairs of Bev(-) and Bev(+) cases were ***: The median duration of follow-up was 15.8 months. The median progression-free survival(PFS) was prolonged significantly in the Bev(+) group than in the Bev(-) group in overall(9.8 vs. 7.8 months, P=0.006) and PSM pairs(9.8 vs. 6.6 months, Pnon-Bev chemotherapy in Chinese patients with advanced NS-NSCLC.

关键词： Bevacizumab pemetrexed non-squamous non-small cell lung cancer maintenance treatment propensity score matching

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Radiomics-based predictive risk score: A scoring system for preoperatively predicting risk of lymph node metastasis in patients with resectable non-small cell lung cancer

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Chinese Journal of Cancer Research 2019年第4期31卷 641-652页

作者： Lan He Yanqi Huang Lixu Yan Junhui Zheng Changhong Liang Zaiyi Liu Department of Radiology Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Pathology Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China

Objective: To develop and validate a radiomics-based predictive risk score(RPRS) for preoperative prediction of lymph node(LN) metastasis in patients with resectable non-small cell lung cancer(NSCLC).Methods: We retrospectively analyzed 717 who underwent surgical resection for primary NSCLC with systematic mediastinal lymphadenectomy from October 2007 to July 2016. By using the method of radiomics analysis, 591 computed tomography(CT)-based radiomics features were extracted, and the radiomics-based classifier was constructed. Then, using multivariable logistic regression analysis, a weighted score RPRS was derived to identify LN metastasis. Apparent prediction performance of RPRS was assessed with its calibration,discrimination, and clinical ***: The radiomics-based classifier was constructed, which consisted of 13 selected radiomics *** models demonstrated that radiomics-based classifier, age group, tumor diameter, tumor location, and CT-based LN status were independent predictors. When we assigned the corresponding score to each variable,patients with RPRSs of 0-3, 4-5, 6, 7-8, and 9 had distinctly very low(0%-20%), low(21%-40%), intermediate(41%-60%), high(61%-80%), and very high(81%-100%) risks of LN involvement, respectively. The developed RPRS showed good discrimination and satisfactory calibration (C-index: 0.785, 95% confidence interval(95% CI):0.780-0.790)Additionally, RPRS outperformed the clinicopathologic-based characteristics model with net reclassification index(NRI) of 0.711(95% CI: 0.555-0.867).Conclusions: The novel clinical scoring system developed as RPRS can serve as an easy-to-use tool to facilitate the preoperatively individualized prediction of LN metastasis in patients with resectable NSCLC. This stratification of patients according to their LN status may provide a basis for individualized treatment.

关键词： Lymph node radiomics risk score CT non-small cell lung cancer

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Correlation study of biological characteristics of non-small cell lung cancer A549 cells after transfecting plasmid by microbubble ultrasound contrast agent

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Asian Pacific Journal of Tropical Medicine 2016年第6期9卷 564-567页

作者： Xuan-Yan Guo Man-Lu Xue-Qing Chen Fan-Ding He Ang-Li Ultrasonic Department Academy of Sciences of Sichuan Province People's Hospital of Sichuan Province Pancreatic Surgery West China Hospital Sichuan University

Objective: To explore the role of the abnormal expression of miRNAs in the development process of non-small cell lung cancer and the feasibility of ultrasound microbubble-mediated gene therapy after transfecting antisense miRNA-224 and miRNA-122 a plasmids into nonsmall cell lung cancer A549 cells. Methods: Antisense miRNA-224 and miRNA-122 a plasmids were transfected into non-small cell lung cancer A549 cells on the optimal ultrasound microbubble mediated condition. We set up a control group. The cell proliferation activity, apoptosis, invasion ability were detected by MTT assay, Annexin V-PE, Transwell invasion experiment and colony formation assay, respectively. Results: The expression of mi RNA-224 decreased and the expression of miRNA-122 a rose after the plasmids of target genes were transfected into non-small cell lung cancer A549 cells, and there were significant differences when compared with those of the control group(P<0.05). After the plasmids of target genes were transfected into A549 cells, the growth of antisense miRNA-224 and miRNA-122 a were inhibited, and the differences were significant as compared with the control group(P < 0.05). Besides, the inhibition of miRNA-122 a group was the most significant and there was statistically significant difference as compared with miRNA-224 group(t =-4.694, P = 0.009). After the plasmids of target genes were transfected into A549 cells, the proportion of apoptotic cells increased, the invasive cells were decreased and the clone ability reduced, and also there was a significant difference as compared with those of the control group(P < 0.05). What's more, the apoptotic peak appeared in miRNA-122 a group. Its invasion ability decreased most obviously(40.25 ± 3.97/visual field), the number of clone ability was 104.93 ± 4.87 and the inhibitory effect was the most obviously. There was statistically significant difference as compared with other groups(P < 0.05). Conclusions: A549 cells transfected by ultrasound micro

关键词： Microbubble ultrasound contrast agent MiR-224 MiR-122a non-small cell lung cancer

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