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China Medical Abstracts(Internal Medicine) 2024年第1期41卷 44-45页

作者：别志欣 Dept Oncol Beijing HospNatl Gerontol CenterInstit Geriatr MedCAMSBeijing 100730

Objective To investigate the efficacy and adverse effects of first-line immunotherapy combined with chemotherapy in elderly patients with small cell lung cancer(SCLC) in population of real world.Methods A total of 148 elderly SCLC patients (age≥65 years old)underwent pathological diagnosis were retrospectively analyzed from January 2013 to June 2023.

关键词： chemotherapy diagnosis SCLC

CYFRA21-1、NSE、CA72-4、ProGRP对小细胞肺癌的诊断价值

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中国医药指南 2024年第3期22卷 47-49页

作者：吴黎平南京明基医院检验科南京210004

目的本研究的目的是评估并比较联合使用细胞角蛋白片段21-1(CYFRA21-1)、神经内分泌特异性酶(NSE)、糖类抗原72-4(CA72-4)以及促胃泌素释放肽(ProGRP)四项肿瘤标志物在小细胞肺癌(SCLC)诊断中的表现,以确定其诊断性能和对提高SCLC诊断... 详细信息

目的本研究的目的是评估并比较联合使用细胞角蛋白片段21-1(CYFRA21-1)、神经内分泌特异性酶(NSE)、糖类抗原72-4(CA72-4)以及促胃泌素释放肽(ProGRP)四项肿瘤标志物在小细胞肺癌(SCLC)诊断中的表现,以确定其诊断性能和对提高SCLC诊断准确性的意义。方法选取2022年3月至2023年2月在我院治疗的90例SCLC患者作为恶性组,选取同期在本院体检结果为健康的90例患者作为对照组。对比四项肿瘤标志物在恶性组、对照组以及恶性组不同临床分期中的表达水平差异,另外评估四项肿瘤标志物在SCLC诊断中的特异度、灵敏度和准确性。结果恶性组CYFRA21-1、NSE、CA72-4、ProGRP水平均高于对照组(P SCLC的诊断准确性。这种综合应用为肺癌诊断提供了更全面的信息,增强了对SCLC的诊断能力,有望成为临床实践中一个重要的辅助方法。

关键词： SCLC 诊断 CYFRA21-1 NSE CA72-4 ProGRP

A non-metabolic function of hexokinase 2 in small cell lung cancer:promotes cancer cell stemness by increasing USP11-mediated CD133 stability

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Cancer Communications 2022年第10期42卷 1008-1027页

作者： Juhong Wang Fei Shao Yannan Yang Wei Wang Xueying Yang Renda Li Hong Cheng Sijin Sun Xiaoli Feng Yibo Gao Jie He Zhimin Lu Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Laboratory of Translational Medicine National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Central Laboratory National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong 518116P.R.China Zhejiang Provincial Key Laboratory of Pancreatic Disease The First Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhouZhejiang 310029P.R.China Cancer Center Zhejiang UniversityHangzhouZhejiang 310029P.R.China

Background:Maintenance of cancer stem-like cell(CSC)stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self-renewal and tumor progression.As a key glycolytic enzyme,hexokinase 2(HK2)plays an instrumental role in aerobic glycolysis and tumor progression.However,whether HK2 directly contribute to CSC stemness maintenance in small cell lung cancer(SCLC)is largely unclear.In this study,we aimed to investgate whether HK2 independent of its glycolytic activity is directly involved in stemness maintenance of CSC in SCLC.Methods:Immunoblotting analyses were conducted to determine the expression of HK2 in SCLC CSCs and their differentiated counterparts.CSC-like properties and tumorigenesis of SCLC cells with or without HK2 depletion or overexpression were examined by sphere formation assay and xenograft mouse model.Immunoprecipitation and mass spectrometry analyses were performed to identify the binding proteins of CD133.The expression levels of CD133-associated and CSC-relevant proteins were evaluated by immunoblotting,immunoprecipitation,immunofluorescence,and immunohistochemistry assay.RNA expression levels of Nanog,POU5F1,Lin28,HK2,Prominin-1 were analyzed through quantitative reverse transcription PCR.Polyubiquitination of CD133 was examined by in vitro or in vivo ubiquitination assay.CD133+cells were sorted by flow cytometry using an anti-CD133 antibody.Results:We demonstrated that HK2 expression was much higher in CSCs of SCLC than in their differentiated counterparts.HK2 depletion inhibited CSC stemness and promoted CSC differentiation.Mechanistically,nonmitochondrial HK2 directly interacted with CD133 and enhanced CD133 expression without affecting CD133 mRNA levels.The interaction of HK2 and CD133 promoted the binding of the deubiquitinase ubiquitin-specific protease 11(USP11)to CD133,thereby inhibiting CD133 polyubiquitylation and degradation.HK2-mediated upregulation of CD133 expression enhanced the expression of cell renewal regulators,SCLC cell stemness,and tumor grow

关键词： HK2 metabolic enzyme non-metabolic function cancer stem-like cell CD133 USP11 ubiquitylation SCLC

Changes of protein expression during tumorosphere formation of small cell lung cancer circulating tumor cells

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Oncology Research 2023年第1期31卷 13-22页

作者： SANDRA STICKLER BARBARA RATH MAXIMILIAN HOCHMAIR CLEMENS LANG LUKAS WEIGL GERHARD HAMILTON Institute of Pharmacology Medical University of ViennaViennaAustria Karl Landsteiner Institute of Lung Research and Pulmonary Oncology Klinik FloridsdorfViennaAustria Department of Trauma Surgery Sozialmedizinisches Zentrum OstDonauspitalViennaAustria Division of Special Anesthesia and Pain Medicine Medical University of ViennaViennaAustria

Small cell lung cancer(SCLC)is frequently disseminated and has a dismal prognosis with survival times of approximately two years.This cancer responds well to initial chemotherapy but recurs within a short time as a globally chemoresistant tumor.Circulating tumor cells(CTCs)are held responsible for metastasis,the extremely high numbers of these cells in advanced SCLC allowed us to establish several permanent CTC cell lines.These CTCs are distinguished by the spontaneous formation of large spheroids,termed tumorospheres,in regular tissue culture.These contain quiescent and hypoxic cells in their interior and are associated with high chemoresistance compared to single cell cultures.Nine CTC lines were compared for their expression of 84 proteins associated with cancer either as single cells or in the form of tumorospheres in Western blot arrays.With the exception of the UHGc5 line,all other CTC lines express EpCAM and lack a complete EpCAM-negative,vimentin-positive epithelial-mesenchymal transition(EMT)phenotype.Upon formation of tumorospheres the expression of EpCAM,that mediates cell-cell adhesion is markedly upregulated.Proteins such as E-Cadherin,p27 KIP1,Progranulin,BXclx,Galectin-3,and Survivin showed variable changes for the distinct CTC cell lines.In conclusion,EpCAM presents the most critical marker for individual SCLC CTCs and the assembly of highly chemoresistant tumorospheres.

关键词： SCLC Spheroid Chemoresistance EpCAM Topotecan Epirubicin

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实用肿瘤学杂志 2024年第1期38卷 17-17页

作者：本刊编辑部不详

论文中需标注3~5个关键词,请务必使用美国国立医学图书馆编辑的最新版《Index Medicus》医学主题词表(MeSH)内所列出的词,也可以通过上网查检索词。如MeSH上尚无相应的主题词,处理办法:(1)选用直接相关的几个主题词进行组配;(2)选用约... 详细信息

论文中需标注3~5个关键词,请务必使用美国国立医学图书馆编辑的最新版《Index Medicus》医学主题词表(MeSH)内所列出的词,也可以通过上网查检索词。如MeSH上尚无相应的主题词,处理办法:(1)选用直接相关的几个主题词进行组配;(2)选用约定俗成的词组或已被本研究领域广泛认同的自由词。中英文关键词不能缩写,必须给出全文,如“SCLC”应标注为“小细胞肺癌”和“Small cell lung cancer”。

关键词：小细胞肺癌自由词医学主题词表 SCLC 主题词检索词

ILF2 cooperates with E2F1 to maintain mitochondrial homeostasis and promote small cell lung cancer progression

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Cancer Biology & Medicine 2019年第4期16卷 771-783页

作者： Meng Zhao Yahui Liu Jiao Chang Jin Qi Ran Liu Yongwang Hou Yanhui Wang Xinwei Zhang Lu Qiao Li Ren Tianjin 300060China Tianjin 300060China Department of Immunology Tianjin Key Laboratory of Cellular and Molecular ImmunologyKey Laboratory of Educational Ministry of ChinaSchool of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China

Objective:Mitochondria play multifunctional roles in carcinogenesis.Deciphering uncertainties of molecular interactions within mitochondria will promote further understanding of cancer.Interleukin enhancer binding factor 2(ILF2)is upregulated in several malignancies,however,much remains unknown regarding ILF2 in small cell lung cancer(SCLC).In the current study,we explored ILF2's role in SCLC and demonstrated its importance in mitochondria quality control.Methods:Colony formation,cell proliferation,cell viability and xenograft studies were performed to examine ILF2's role on SCLC progression.Glucose uptake,lactate production,cellular oxygen consumption rate and extracellular acidification rate were measured to examine the effect of ILF2 on glucose metabolism.RNA-sequencing was utilized to explore genes regulated by ILF2.E2 F1 transcriptional activity was determined by dual luciferase reporter assay.Mitochondria quantification and mitochondrial membrane potential assays were performed to examine mitochondrial quality.Gene expression was determined by RT-qPCR,Western blot and IHC assay.Results:ILF2 promotes SCLC tumor growth in vitro and in vivo.ILF2 elevates oxidative phosphorylation expression and declines glucose intake and lactate production.Genome-wide analysis of ILF2 targets identified a cohort of genes regulated by E2 F1.In consistent with this,we found ILF2 interacts with E2 F1 in SCLC cells.Further studies demonstrated that suppression of E2 F1 expression could reverse ILF2-induced tumor growth and enhanced mitochondria function.Significantly,expression of ILF2 is progressively increased during SCLC progression and high ILF2 expression is correlated with higher histologic grades,which indicates ILF2's oncogenic role in SCLC.Conclusions:Our results demonstrate that ILF2 interacts with E2 F1 to maintain mitochondria quality and confers SCLC cells growth advantage in tumorigenesis.

关键词： E2F1 OXPHOS mitochondria metabolism SCLC

PI3K/Akt/mTOR signaling orchestrates the phenotypic transition and chemo-resistance of small cell lung cancer

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Journal of Genetics and Genomics 2021年第7期48卷 640-651页

作者： Xuefeng Li Cheng Li Chenchen Guo Qiqi Zhao Jiayu Cao Hsin-Yi Huang Meiting Yue Yun Xue Yujuan Jin Liang Hu Hongbin Ji State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100049China Department of Medical Oncology The First Affiliated HospitaHengyang MedicalSchoolUniversity of South ChinaHengyangHunan 421001China School of Life Science and Technology Shanghai Tech UniversityShanghai 200120China CAS Key Laboratory of Computational Biology CAS-MPG Partner Institute for Computational BiologyShanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China

Small cell lung cancer(SCLC)is a phenotypically heterogeneous disease with an extremely poor prognosis,which is mainly attributed to the rapid development of resistance to chemotherapy.However,the relation between the growth phenotypes and chemo-resistance of SCLC remains largely unclear.Through comprehensive bioinformatic analyses,we found that the heterogeneity of SCLC phenotype was significantly associated with different sensitivity to chemotherapy.Adherent or semiadherent SCLC cells were enriched with activation of the PI3K/Akt/mTOR pathway and were highly chemoresistant.Mechanistically,activation of the PI3K/Akt/mTOR pathway promotes the phenotypic transition from suspension to adhesion growth pattern and confers SCLC cells with chemo-resistance.Such chemo-resistance could be largely overcome by combining chemotherapy with PI3K/Akt/mTOR pathway inhibitors.Our findings support that the PI3K/Akt/mTOR pathway plays an important role in SCLC phenotype transition and chemo-resistance,which holds important clinical implications for improving SCLC treatment.

关键词： SCLC Heterogeneity Growth pattern Phenotype transition Drug resistance PI3K/Akt/mTOR pathway

p53 Gene Mutations in Asbestos Associated Cancers

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Biomedical and Environmental Sciences 1998年第3期11卷 226-232页

作者： LIU BING-CI FU DE-CHEN MIAO QING WANG HAI-HUA AND YOU BAO-RONG (Institute of Occupotional theicine, Chinese Academy of Preventive Medicine, Beijing 100050, China) Institute of Occupational Medicine Chinese Academy of Preventive Medicine Beijing China.

The accumulation of mutant p53 protein in cancer cells was observed by immunohistochemistry analysis. DNA was extracted from paraffin-embedded tissue. Exons 5, 7 and 8 were amplified and studied by PCR-SSCP and sequencing analysis. Ten cases of asbestos associated cancer tissue were studied, of which five cases had adenocarcinoma, and the other five had mesothelioma, squamous carcinoma, small cell lung cancerl adenosquamous carcinoma and malignant lymphoma respectively. Employing monoclonal antibody PAb1801, five cases were found to be mutant p53 protein mpitive. Seven cases were found to have mutations by PCRSSCP. A total of 7 cases (8 mutations) were found to be positive and 4 cases were found to be opitive by both of these analyses. Of the 8 mutations found by SSCP analysis, 4(50%, 4/8)were clustered in exon 8. A high mutation frequency was noticed in adenocarcinoma (80%,4/5). ffequencing analysis on two specimens revealed two hotspot mutations. In codon 234,TAC for tyrooin was mutated to AAC fOr aspar8gine by a T to A transversion of the first letter. In codon 273, CGT for arginine was mutated to AGT for serine by a C to A transversion of the first letter. ln conclusion, the mutation of p53 gene is common in asbestos associated cancers. However, the mutational spectrum of asbestos associated cancers might be different from that of non-asbestos associated cancers.

关键词： gene Gene SCLC p53 Gene Mutations in Asbestos Associated Cancers

Estimation of electron mobility of n-doped 4,7-diphenyl-1,10-phenanthroline using space-charge-limited currents

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Journal of Semiconductors 2009年第11期30卷 63-66页

作者：希扎尔.乌尔.哈克鲁富翰蒋雪茵张志林张小文张良李俊 School of Materials Science and Engineering Shanghai University Key Laboratories of Advanced Display and System Applications Ministry of EducationShanghai University

The electron mobilities of 4, 7-diphenyl-1, 10-phenanthroline （BPhen） doped 8-hydroxyquinolinatolithium （Liq） at various thicknesses （50-300 nm） have been estimated by using space-charge-limited current measurements. It is observed that the electron mobility of 33 wt% Liq doped BPhen approaches its true value when the thickness is more than 200 rim. The electron mobility of 33 wt% Liq doped BPhen at 300 nm is found to be -5.2 × 10^-3 cm^2/（V.s）（at 0.3 MV/cm） with weak dependence on electric field, which is about one order of magnitude higher than that of pristine BPhen （3.4 × 10^-4 cm^2/（V.s）） measured by SCLC. For the typical thickness of organic light-emitting devices, the electron mobility of doped BPhen is also investigated.

关键词： doping electron mobility SCLC 8-hydroxyquinolinonate-lithium （Liq）

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溶瘤病毒在肺癌治疗中的研究进展

中国呼吸与危重监护杂志 2022年第5期21卷 374-380页

作者：林希向莉苹阳一黄娜成都医学院第一附属医院呼吸与危重症医学科四川成都610500

肺癌是最常被诊断的癌症之一,也是全球癌症相关死亡的主要原因,每年有220万新发的肺癌患者和190万人死于肺癌。在2020年,在新发癌症中,肺癌约占11.4%,造成约18.0%的癌症相关性死亡。根据肺癌的组织学亚型,肺癌可进一步分为小细胞肺癌(sm... 详细信息

肺癌是最常被诊断的癌症之一,也是全球癌症相关死亡的主要原因,每年有220万新发的肺癌患者和190万人死于肺癌。在2020年,在新发癌症中,肺癌约占11.4%,造成约18.0%的癌症相关性死亡。根据肺癌的组织学亚型,肺癌可进一步分为小细胞肺癌(small cell lung cancer,SCLC)和非小细胞肺癌(non-small cell lung cancer,NSCLC),分别占总诊断的15%和总诊断的85%。

关键词：肺癌治疗溶瘤病毒非小细胞肺癌组织学亚型 SCLC 癌症小细胞肺