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Bronchial Fistula: Rare Complication of Treatment with Anlotinib

中国肺癌杂志 2020年第10期23卷 858-865页

作者： Pengbo DENG chengping hu Yuanyuan LI Liming CAO huaping YANG Min LI Jian AN Juan JIANG Qihua GU Department of Respiratory Medicine Xiangya Lung Cancer Center Xiangya HospitalCentral South UniversityChangsha 410008China

Background and objective Anlotinib is a newly developed small molecule multiple receptor tyrosine kinase(RTK) inhibitor that was approved for the treatment of patients with lung cancer in China. We aim to report 3 cases of rare complication of anlotinib-bronchial fistula(BF) during the treatment of lung cancer patients and summarize the possible *** We collected three patients who developed BF due to anlotinib treatment, and conducted a search of Medline and Pub Med for medical literature published between 2018 and 2020 using the following search terms: "anlotinib," "lung cancer," and "fistula."Results Our literature search produced two case reports(three patients) which, in addition to our three patients. We collated the patients’ clinical characteristics including demographic information, cancer type, imaging features, treatment received, risk factors for anlotinib related BF, and treatment-related outcomes. The six patients shared some common characteristics: advanced age, male, concurrent infection symptoms, diabetes mellitus(DM), advanced squamous cell and small cell lung cancers, centrally located tumors, tumor measuring ≥5 cm in longest diameter, and newly formed tumor cavitation after multi-line treatment especially after receiving radiotherapy. Fistula types included broncho-pericardial fistula, broncho-pleural fistula, and esophagotracheobronchial fistula. Six patients all died within 6 *** Although anlotinib is relatively safe, it is still necessary to pay attention to the occurrence of BF, a rare treatment side effect that threatens the quality of life and overall survival of patients. Anlotinib, therefore, requires selective use and close observation of high-risk patients.

关键词： lung cancer fistula

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Low-intensity aerobic exercise training attenuates airway inflammation and remodeling in a rat model of steroid-resistant asthma

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Chinese Medical Journal 2014年第17期127卷 3058-3064页

作者： Qin Qingwu Chen Xi Feng Juntao Qin Ling hu chengping Department of Respiratory Medicine Xiangya Hospital Central South University National Clincial Research Center for Respirator3[ Disease Changsha Hunan 410008 China Bronchial Asthma Research Center of hunan Province Changsha Hunan 410008 China

Background Aerobic exercise can improve symptoms,reduce airway inflammation,and even ameliorate airway remodeling in asthmatic animals and ***,previous studies have focused mainly on the effect of aerobic exercise on steroid-sensitive asthma （SSA）.The goals of this study were to determine the effect of low-intensity aerobic exercise training on airway hyperresponsiveness,inflammation,and remodeling in a rat model of steroid-resistant asthma （SRA） and to identify the potential mechanisms underlying these *** Endotoxin-free ovalbumin with or without lipopolysaccharide were applied to establish rat models of SRA and SSA,*** hyperresponsiveness,inflammation,remodeling,expression of interleukin （IL）-25,IL-33,thymic stromal lymphopoietin （TSLP）,high mobility group box-1 （HMGB1）,and IL-17 in bronchoalveolar lavage fluid （BALF）,and the role of dexamethasone （DXM） were compared between these two asthmatic rat *** effect of low-intensity aerobic exercise training and anti-HMGB1 treatment on airway hyperresponsiveness,inflammation,and remodeling in SRA rats also was *** SRA rats developed neutrophil-dominated airway inflammation （（29.5±4.1）％ of the total cell numbers in BALF）,whereas SSA rats developed eosinophil-dominated airway inflammation （（24.0±6.1）％ of the total cell numbers in BALF）.Compared with SSA rats,SRA rats had more severe airway hyperresponsiveness,lower levels of IL-25 （（33.6±10.3） vs.（104.8±24.9） pg/ml）,IL-33 （（87.5±25.0） vs.（226.6±40.7） pg/ml）,and TSLP （（1 933.2±899.5） vs.（7 224.0±992.1） pg/ml）,and higher levels of HMGB1 （（21.2±4.5） vs.（5.4±1.6） ng/ml） and IL-17 （（780.5±261.7） vs.（291.4±76.4） pg/ml） in BALF （all P ＜0.05）.However,there was no significant difference in goblet cell hyperplasia,subepithelial collagen thickness,and airway smooth muscle remodeling between the two *** with control SSA rats,airway hyperresponsiveness,inflammation,and remodeling in SRA rats were less sensitive t

关键词： aerobic exercise inflammation airway remodeling steroid-resistant asthma high mobility group box-1

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Theanine improves the function of dendritic cells via the downregulation of cyclooxygenase-2 expression

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Chinese Medical Journal 2014年第8期127卷 1545-1549页

作者： Lei Mingsheng Zuo Jianhong Li Min Gu Qihua hu chengping Department of Respiratory and Critical Care Medicine Xiangya Hospital Central South University Changsha Hunan 410008 China Department of Respiratory and Critical Care Medicine Zhangiiajie City Hospital Zhangjiajie Hunan 427000 China Medical School University of South China Hengyang Hunan 421001 China

Background Tumor cells can reduce the number of dendritic cells （DCs） in the tumor environment and cause DC dysfunction through autocrine or paracdne pathways. We sought to measure cyclooxygenase-2 （COX-2） expression in bombesin-inhibited DCs treated with theanine in vitro and to explore the protection and activation effects of theanine on DCs. Methods Enzyme-linked immunosorbent assay （ELISA）, reverse transcription-polymerase chain reaction （RT-PCR）, and Western blotting were used to analyze the effects of theanine on COX-2 expression and interleukin （IL）-12/IL-10 secretion of bombesin-treated DCs. Results DCs acquired an impaired phenotype as a result of bombesin treatment. Theanine increased the expression of mature DC surface molecules. The number of cell apoptosis with the treatment of bombesin and theanine significantly decreased, accounting for 15.9%, compared with 26.1% of cell apoptosis with bombesin. COX-2 expression in bombesin- treated DCs was inhibited by theanine in a dose-dependent manner. Theanine promoted DC secretion of IL-12. IL-12 levels reached （137.4_＋4.9） pg/ml with theanine at 200 pmol/L. However, theanine inhibited the secretion of IL-10 in a dose-dependent manner. IL-10 levels were only （58.4_＋6.9） pg/ml with theanine at 200 IJmol/L. Conclusion Theanine inhibits the transcription and translation of COX-2 and regulates the balance of IL-10/IL-12 secretion in bombesin-inhibited DCs, leadincl to the recovery of a state of activation in DCs.

关键词： theanine dendritic cells bombesin cyclooxygenase-2

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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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Fluorofenidone Attenuates Bleomycin-Induced Pulmonary Inflamation and Fibrosis in Mice via Restoring Caveolin-1 Expression and Inhibiting MAPK Signaling Pathway

Fluorofenidone Attenuates Bleomycin-Induced Pulmonary Inflam...

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中华医学会呼吸病学年会——2013（第十四次全国呼吸病学学术会议）

作者： Jie Meng Yeqiang Zou chengping hu Department of Pulmonary Medicine Xiangya Hospital

Idiopathic pulmonary fibrosis(IPF) is a progressive, life-threatening,interstitial lung disease with no effective *** this study,we evaluated the effects of fluorofenidone(FD),a novel pyridone agent,on a murine model of bleomycin(BLM)-induced pulmonary inflammation and *** for Cancer Research (ICR) mice were intravenously injected with BLM or saline(SA) for 14 consecutive ***,pirfenidone (PD)(500 mg·kg·day,respectively) or vehicle was administered by gastrogavage one day before

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脑转移肿瘤细胞及其微环境

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中国肺癌杂志 2016年第9期19卷 626-635页

作者：钟文胡成平中南大学湘雅医院呼吸内科长沙410008

近年来,随着早期诊断的方法的出现及精准治疗的应用,肺癌患者的生存及生活质量都得到很大改善。然而,对于肺癌的脑转移病灶,目前仍缺乏一个理想的治疗方案,严重影响了该部分患者生存状态。了解肿瘤细胞如何在中枢神经系统定植、生长和... 详细信息

近年来,随着早期诊断的方法的出现及精准治疗的应用,肺癌患者的生存及生活质量都得到很大改善。然而,对于肺癌的脑转移病灶,目前仍缺乏一个理想的治疗方案,严重影响了该部分患者生存状态。了解肿瘤细胞如何在中枢神经系统定植、生长和侵袭等相关生物学行为及其产生机制对预防及治疗肿瘤细胞脑转移病灶具有重大的意义。"种子-土壤"这一假说可以很好的解释这一过程,这一假说的关键即肿瘤细胞可与中枢神经系统微环境各组成之间产生相互适应性变化,正是这种相互作用决定了脑转移病灶的发生发展。本文就脑转移肿瘤细胞、脑转移肿瘤微环境及他们之间的相互作用进行综述,旨在为脑转移病灶的治疗提供新的思路。

关键词：肿瘤脑转移肿瘤微环境星形胶质细胞少突胶质细胞血脑屏障血管形成

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The effect of Tai Chi on lung function,exercise capacity and diaphragm strength in people with Chronic Obstructive Pulmonary Disease

The effect of Tai Chi on lung function,exercise capacity and...

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中华医学会呼吸病学年会——2013（第十四次全国呼吸病学学术会议）

作者： Ruichao Niu Ruoxi He Bailing Luo chengping hu Department of Respiratory Medicine Xiangya Hospital of Central South University

Background Although the benefits of exercise on the health of patients with COPD have been widely reported, the effect of Tai Chi as an alternative exercise has not been well evaluated in patients with *** study reported a randomized controlled trial,which investigated the effect of Tai Chi on lung function, exercise capacity,and diaphragm strength in patients with COPD. Methods 40 patients with COPD were randomized into the control group and Tai Chi *** in the

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非小细胞肺癌EGFR-TKI治疗临床获益后颅内转移机制研究进展

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中国肺癌杂志 2015年第8期18卷 518-522页

作者：蒋娟胡成平中南大学湘雅医院呼吸科长沙410008

表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor,EGFRTKI)广泛用于治疗EGFR突变阳性的非小细胞肺癌(non-small cell lung cancer,NSCLC)。然而,部分患者在接受EGFR-TKI治疗后、原发病灶稳定甚至缩小的同时,却出现了新发颅内转移灶或者原有颅内病灶进展,其机制未明。近年来多项研究表明,这种现象可能与EGFR-TKI的药物代谢动力学、NSCLC原发灶与转移灶的异质性、EGFR突变本身特质及患者生存期的延长有关。因此,本文就NSCLC患者在EGFR-TKI治疗临床获益后发生颅内转移的相关机制研究进展作一综述。

关键词：表皮生长因子受体酪氨酸激酶抑制剂肺肿瘤颅内转移

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重症肺炎患者的机械通气脱机的影响因素

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中南大学学报（医学版） 2015年第1期40卷 107-111页

作者：阎昱升胡成平中南大学湘雅医院呼吸内科长沙410008

目的:分析影响重症肺炎患者机械通气成功脱机的危险因素。方法:回顾性分析长沙市第一医院呼吸科从2011年6月至2013年12月因重症肺炎合并呼吸衰竭需要有创机械通气的患者共59例。入选患者根据最后结局分为脱机成功组(n=31)和脱机失败组(n... 详细信息

目的:分析影响重症肺炎患者机械通气成功脱机的危险因素。方法:回顾性分析长沙市第一医院呼吸科从2011年6月至2013年12月因重症肺炎合并呼吸衰竭需要有创机械通气的患者共59例。入选患者根据最后结局分为脱机成功组(n=31)和脱机失败组(n=28)。分别记录两组患者入院开始的一般资料、实验室检查、细菌学结果。将所有指标进行单因素比较和Logistic回归分析以了解其对机械通气脱机的影响。结果:单因素分析表明:两组患者在性别与年龄上差异无统计学意义(均P>0.05),脱机成功组在吸烟人数、APACHE II评分、D-二聚体和脑尿钠肽(brain natriuretic peptide,BNP)的浓度方面明显低于失败组,差异均有统计学意义(均P<0.05)。脱机成功组在进入重症监护病房时血清白蛋白水平均高于失败组,两组间比较差异均有统计学意义(均P<0.05)。所有因素进行Logistic回归分析后表明,D-二聚体的升高、肺部CT存在肺部基础疾病、低白蛋白是重症肺炎机械通气脱机的独立的危险因素。结论:对存在低蛋白血症、高D-二聚体及肺部CT存在肺部基础疾病的重症肺炎患者进行综合评估和治疗,有利于上述患者成功脱机。

关键词：重症肺炎机械通气影响因素

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吉非替尼可能通过EGFR启动子甲基化诱导肺腺癌细胞继发性耐药

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中国肺癌杂志 2015年第4期18卷 193-198页

作者：王起龙李敏胡成平中南大学湘雅医院呼吸内科长沙410008

背景与目的在肺腺癌靶向治疗中的吉非替尼继发性耐药是临床遇到的重要问题。本研究旨在探讨吉非替尼是否可诱导肺腺癌PC9细胞发生继发性耐药,以及表皮生长因子受体(epidermal growth factor receptor,EGFR)启动子甲基化在耐药过程中的作... 详细信息

背景与目的在肺腺癌靶向治疗中的吉非替尼继发性耐药是临床遇到的重要问题。本研究旨在探讨吉非替尼是否可诱导肺腺癌PC9细胞发生继发性耐药,以及表皮生长因子受体(epidermal growth factor receptor,EGFR)启动子甲基化在耐药过程中的作用,拟为肺腺癌耐药提供新的治疗靶点。方法体外培养肺腺癌吉非替尼敏感细胞株PC9,应用不同浓度吉非替尼进行干预。MTT法检测PC9细胞株对吉非替尼的敏感性。亚硫酸氢盐处理后测序法(bisulfite sequencing polymerase chain reaction,BSP)检测肺腺癌PC9细胞株EGFR启动子甲基化水平。使用5-氮杂-2’-脱氧胞苷(5-Aza-dc)对吉非替尼耐药细胞株PC9/GR细胞株进行干预。MTT法检测耐药株PC9/GR对吉非替尼敏感性的变化。结果经过从0.01μmol/L逐渐提升吉非替尼诱导浓度至3μmol/L之后,MTT显示耐药细胞株PC9/GR细胞株半抑制浓度(half maximal inhibitory concentration,IC50)[(3.95±0.23)μmol/L]较之前敏感株PC9[(0.01±0.002)μmol/L]明显升高(P<0.05),BSP显示发生异常甲基化的位点结果比较:PC9/GR甲基化水平明显升高(74%vs59%,P<0.05)。RT-PCR显示PC9/GR细胞株较PC9细胞株EGFR m RNA表达量升高(P<0.05)。使用5-Aza-dc处理PC9/GR细胞后,PC9/GR细胞株IC50较对照组降低[(2.55±0.14)μmol/L vs(3.87±0.034)μmol/L,P<0.05)]。结论吉非替尼体外浓度递增诱导法可诱导PC9细胞株产生吉非替尼继发性耐药,成功构建PC9/GR耐药细胞株。PC9细胞EGFR启动子甲基化异常可能参与了吉非替尼继发性耐药机制。

关键词：肺肿瘤酪氨酸激酶抑制剂继发性耐药表皮生长因子受体甲基化

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