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Peripheral blood indices to predict PFS/OS with anlotinib as a subsequent treatment in advanced small-cell lung cancer

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Cancer Biology & Medicine 2022年第8期19卷 1249-1258页

作者： Cuicui Zhang Jing Wang Xinyue Wang Zhaoting Meng Ying Cheng Kai Li Department of Thoracic Oncology Tianjin Medical University Cancer Institute and HOSpital National Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Jilin Cancer HOSpital Changchun 130021China

Objective:In the phase II ALTER-1202(NCT03059797)trial,anlotinib significantly improved progression-free survival(PFS)and overall survival(OS)in patients with advanced small-cell lung cancer(SCLC)who underwent at least 2 previous chemotherapy cycles,when compared with a placebo group.To identify potential factors for predicting efficacy and prognOSis with anlotinib treatment,we analyzed hematological indices at baseline and adverse events(AEs)over the course of anlotinib treatment.Methods:Data were collected from March 2017 to April 2019 from a randomized,double-blind,placebo-controlled,multicenter,phase II trial of anlotinib.Eligible patients were randomly assigned 2:1 to receive anlotinib or placebo until disease progression,intolerable toxicity,or withdrawal of consent.The patients received anlotinib(12 mg)or an analogue capsule(placebo)orally once daily for 14 days every 3 weeks.The hematological indices at baseline and AEs that occurred in the initial 2 treatment cycles were recorded.The Kaplan-Meier test and Cox regression model were used to assess survival differences.Results:A total of 82 patients(81 patients with complete data)were randomly assigned to receive anlotinib,with 38 receiving a placebo as a control.Multivariate analysis indicated that an elevated neutrophil to lymphocyte ratio>7.75 and lactate dehydrogenase>254.65 U/L at baseline were independent risk factors for PFS;basal elevated aspartate aminotransferase>26.75 U/L,neuron specific enolase>18.64 ng/mL,and fibrinogen>4.645 g/L were independent risk factors for OS.During treatment,elevatedγglutamyltransferase and hypophOSphatemia were independent predictors for a poor PFS,and elevatedγ-glutamyl transferase and hypercholesterolemia were independent factors for OS.Conclusions:Our study preliminarily defined potential factors that affected the PFS and OS at baseline and during anlotinib treatment in patients with advanced SCLC.Our findings provide a basis for screening the dominant population and for dynamic efficacy monitoring with anlotinib th

关键词： Small-cell lung cancer anlotinib predictive factors PFS OS

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Per OS infectivity factors:a complicated and evolutionarily conserved entry machinery of baculovirus

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Science China(Life Sciences) 2017年第8期60卷 806-815页

作者： Xi Wang Xiaoping Liu George Alliwa Makalliwa Jiang Li Hualin Wang Zhihong Hu Manli Wang State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China University of Chinese Academy of Sciences Beijing 100049China

Baculoviruses are a family of arthropod-specific large DNA viruses that infect insect species belonging to the orders Lepidoptera,Hymenoptera and Diptera.In nature,occlusion-derived viruses(ODVs) initiate baculovirus primary infection in the midgut epithelium of insect hOSts,and this process is largely dependent on a number of ODV envelope proteins designated as per OS infectivity factors(PIFs).Interestingly,PIF homologs are also present in other invertebrate large DNA viruses,which is indicative that per OS infection is an ancient and phylogenetically conserved entry mechanism shared by these viruses.Here,we review the advances in the knowledge of the functions of individual PIFs and recent discoveries about the PIF complex,and discuss the evolutionary implications of PIF homologs in invertebrate DNA viruses.Furthermore,future research highlights on the per OS infection mechanism are also prOSpected.

关键词：杆状病毒病毒感染感染机制 OS 保守进化 DNA病毒 PIFS

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Understanding “software-defined” from an OS perspective: technical challenges and research issues

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Science China(Information Sciences) 2017年第12期60卷 271-273页

作者： Hong MEI Beijing Institute of Technology Key Laboratory on High-Confidence Software Technologies(MOE) Peking University

What is"software-defined"?Software-defined has become one of the hottest buzzwords in the information technology(IT)community.It is used to describe a family of technologies,including software-defined networking(SDN),softwaredefined storage(SDS),and software-defined data centers(SDDC).These are part of a broader trend that is referred to as software-defined everything

关键词： OS from an OS perspective Understanding software-defined technical challenges and research issues

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节律基因NPAS2在鼻咽癌中的预后生存价值及意义

节律基因NPAS2在鼻咽癌中的预后生存价值及意义

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作者：梁鑫贵州医科大学

学位级别：硕士

目的:通过免疫组化方法检测鼻咽癌中NPAS2蛋白的表达,分析NPAS2蛋白表达与Ki-67蛋白表达、临床特征、肿瘤分期、近期疗效和生存之间的关系,探究NPAS2基因在预测鼻咽癌患者预后生存的价值。方法:收集106例鼻咽癌和31例鼻咽慢性炎症组织... 详细信息

目的:通过免疫组化方法检测鼻咽癌中NPAS2蛋白的表达,分析NPAS2蛋白表达与Ki-67蛋白表达、临床特征、肿瘤分期、近期疗效和生存之间的关系,探究NPAS2基因在预测鼻咽癌患者预后生存的价值。方法:收集106例鼻咽癌和31例鼻咽慢性炎症组织患者的组织蜡块,再通过免疫组化方法检测NPAS2蛋白的表达值,分析其在癌组织及炎症组织中的表达差异。同时收集患者的临床病历资料(年龄,性别、TNM分期等)并收集了70例鼻咽癌患者的Ki-67数据,所有鼻咽癌患者均采取同步放化疗联合诱导化疗或辅助化疗。诱导化疗方案包括(多西他赛+顺铂+氟尿嘧啶;吉西他滨+顺铂)辅助化疗方案包括(顺铂+氟尿嘧啶;吉西他滨+顺铂)。同步化疗方案包括紫杉醇或顺铂;放疗均采用调强放射治疗,接受根治剂量。使用受试者工作特征曲线(ROC)计算NPAS2蛋白表达及Ki67蛋白表达的临界值,分析二者与临床特征以及预后的相关性,Spearman方法分析NPAS2与Ki67相关性。结果:NPAS2蛋白在鼻咽癌中为低表达,表达值为91.532±55.106,在鼻咽炎性组织中为高表达,表达值为131.667±36.586,差异具体一定统计价值(POS(Overall Survival)、PFS(Progression-free Survival)高于低表达组,差异具有统计学意义(POS、PFS高于N2-3期、M1期、IVa-IVb期(POS、PFS低于Ki-67低表达1,3年的OS、PFS,与性别、年龄、T分期等均无关(P>0.05)。COX多因素分析提示鼻咽癌细胞中NPAS2蛋白、N分期、M分期分别是OS的独立影响因子,而与Ki-67蛋白、性别、年龄、T分期、治疗方案等无关。Spearman分析发现NPAS2与OS正相关(POS负相关(POS、PFS延长且高于NPAS2低表达组的OS、PFS;4.3 NPAS2蛋白和OS正相关,NPAS2蛋白与Ki-67蛋白负相关,Ki-67蛋白与OS呈负相关;4.4 NPAS2蛋白是OS的独立预后因素,NPAS2基因在鼻咽癌中可能作为抑癌基评估患者预后生存的指标。

关键词：鼻咽癌时钟基因NPAS2 OS PFS Ki-67

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POSterior ankle impingement–an underdiagnOSed cause of ankle pain in pediatric patients

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World Journal of Orthopedics 2019年第10期10卷 364-370页

作者： Indranil Kushare Kristen Kastan Sachin Allahabadi Department of Orthopaedics Texas Children’s hospitalThe WoodlandsTX 77384United States Department of Orthopaedics University of CaliforniaSan FranciscoCA 94143United States

BACKGROUND POSterior ankle impingement syndrome(PAIS)is a cause of ankle pain due to pinching of bony or soft tissue structures in the hindfoot.The diagnOSis is primarily made based on detailed history and accurate clinical examination.The delay in its diagnOSis has not yet been described in the pediatric and adolescent population.AIM To identify and characterize misdiagnOSed cases of PAIS in pediatric and adolescent patients.METHODS This descriptive prOSpective study at a tertiary children’s hOSpital included patients≤18 years who underwent pOSterior ankle arthrOScopy after presenting with chronic pOSterior ankle pain after being diagnOSed with PAIS.Collected data included:Demographics,prior diagnOSes and treatments,providers seen,time to diagnOSis from presentation,and prior imaging obtained.Visual Analogue Scale(VAS)for pain and American Orthopedic Foot Ankle Society(AOFAS)ankle-hindfoot scores were noted at initial presentation and follow-up.RESULTS 35 patients(46 ankles)with average age of 13 years had an average 19 mo(range 0-60 mo)delay in diagnOSis from initial presentation.25(71%)patients had previously seen multiple medical providers and were given multiple other diagnOSes.All 46(100%)ankles had tenderness to palpation over the pOSterior ankle joint.Radiographs were reported normal in 31/42(72%)exams.In 32 ankles who underwent MRI,the mOSt common findings included OS trigonum(47%)/Stieda process(47%).Conservative treatment had already been attempted in all patients.Ankle impingement pathology was confirmed during arthrOScopy in 46(100%)ankles.At an average follow-up of 13.1 mo,there was an improvement of VAS(pre-op 7.0 to pOSt-op 1.2)and AOFAS scores(pre-op 65.1 to pOSt-op 94).CONCLUSION This is the first study which shows that PAIS is a clinically misdiagnOSed cause of pOSterior ankle pain in pediatric and adolescent population;an increased awareness about this diagnOSis is needed amongst providers treating young patients.

关键词： Ankle impingement Ankle pain OS trigonum Delayed diagnOSis Ankle arthrOScopy Pediatric

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PrognOStic evaluation of pOStoperative adjuvant therapy for operable cervical cancer:10 years'experience of National Cancer Center in China

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Chinese Journal of Cancer Research 2017年第6期29卷 510-520页

作者： Tong Shu Dan Zhao Bin Li Yating Wang Shuanghuan Liu Pingping Li Jing Zuo Ping Ba i RongZhang Lingying Wu Department of Gynecologic Oncology National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective： The aim of this study was to investigate the prognOStic factors and to evaluate the impact of adjuvant therapy on clinical outcome for early-stage cervical cancer. Methods： The clinical-pathological data of all 1,335 patients with the International Federation of Gynecology and Obstetrics （FIGO） Ib-[Ia cervical cancer treated with primary radical surgery at the Chinese National Cancer Center between May 2007 and Dec 2013 were retrOSpectively reviewed. The median follow-up was 70 months. Results： Of all the patients, 61.6% of the cases received adjuvant therapy, with 5-year disease-free survival （DFS） of 92.1% and 5-year overall survival （OS） of 95.0%. In multivariate analysis, differentiation of G3 （P〈0.05）, lymph node metastasis （LNM, P〈0.05） and lymphovascular space invasion （LVSI, P〈0.05） were independent predictors for OS, while LNM （P〈0.05）, deep stroma invasion （DSI, P〈0.05） and LVSI （P〈0.05） were independent factors for DFS. The samples were stratified by histologic type, and cervical squamous cell carcinoma （SCC） was found to share the same independent factors except for differentiation of OS. As to patients with cervical adenocarcinoma/adenOSquamons carcinoma （AC/ASC）, differentiation was the independent predictor of OS （P〈0.05）; and LVSI of DFS （P〈0.05）. Of 236 patients with high-risk factors, there was no significant difference in survival between concurrent chemoradiotherapy （CCRT, n=195）, radiotherapy （RT, n=24）, and chemotherapy （CT, n=17）. Among the 190 patients with LNM who underwent CCRT, 124 cases showed improved DFS after sequential CT （P=0.118）, with a recurrence rate decrease of 14%, though the difference was not statistically significant. Patients with single intermediate-risk factors like DSI or LVSI were found to partially benefit from adjuvant therapy, but the difference was not statistically significant. Conclusions： LNM, LVSI, DSI and differentiation were found to be independent prognOStic factors for operable cervical cancer. Aggressive pOStoperative adjuvant therapy based on

关键词： Cervical neoplasm adjuvant therapy prognOStic factors DFS OS

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The ascent of immune checkpoint inhibitors： is the understudy ready for a leading role？

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Cancer Biology & Medicine 2017年第4期14卷 341-347页

作者： Amy L. Cummings Edward B. Garon Department of Hematology and Oncology David Geffen School of Medicine at the University of California Los Angeles 90095 USA

The recent approval of pembrolizumab as second-line treatment for any solid tumor with high-level micrOSatellite instability or mismatch repair deficiency agnOStic of tissue and origin1 has shattered a glass ceiling for immune checkpoint inhibitors.No longer bound to a specific cancer diagnOSis but rather a biomarker,pembrolizumab has heightened a burgeoning optimism towards the drug class.Yet how these agents should carve out additional

关键词： PD The ascent of immune checkpoint inhibitors:is the understudy ready for a leading role PFS OS ORR IHC

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Identification of Abnormal 51 CTA/CTG Expansion as Probably the Shortest Pathogenic Allele for Spinocerebellar Ataxia-8 in China

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NeurOScience Bulletin 2018年第5期34卷 859-862页

作者： Minjin Wang Shuo Guo Wencong Yao Jun Wang Jianxia Tao Yanbing Zhou Binwu Ying Department of Laboratory Medicine West China HospitalSichuan University

Spinocerebellar ataxias （SCAs） are a group of genetic disorders characterized by slowly progressive incoordina- tion of gait and are often associated with poor coordination of the hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. The genetic forms of ataxia are diagnOSed by family history, physical examina- tion, neuroimaging, and molecular genetic testing. At present, 36 SCA subtypes including 27 pathogenic genes have been identified [1]. Different subtypes of SCAs have clear distribution differences among ethnic populations, and SCA8 is an infrequent entity worldwide, which has mOStly been reported in Japanese, but has never been reported in Chinese [2]. SCAB involves bidirectional expression based on the total number of both the （CTA）n and （CTG）n expansion transcripts in ATXN8OS. The pathogenesis of this disorder is complex and the spectrum of clinical presentations is broad. It is predominantly characterized by drawn-out slowness of speech and gait instability, followed by slowly progressive ataxia, with disease onset typically occurring in adulthood [3]. How- ever, the lowest full-penetrance allele for SCA8 onset remains elusive and the current understanding of the phenotypic and genotypic features of SCA8 is limited. Since SCA8 has not yet been reported in the Chinese population and is scantily reported in a small proportion of pedigrees so far, clinical knowledge is still developing. Moreover, the boundary between the normal and patho- genic alleles of SCA8 is uncertain. Here we report the clinical and molecular genetic characteristics of 3 Chinese SCA8 families and have identified 51 CTA/CTG repeats within ATXN8OS, probably the shortest pathogenic allele for SCA8.

关键词： CTG OS CTA Identification of Abnormal 51 CTA/CTG Expansion as Probably the Shortest Pathogenic Allele for Spinocerebellar Ataxia-8 in China

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CD163肿瘤相关巨噬细胞在局部晚期鼻咽癌中的远期预后价值

CD163肿瘤相关巨噬细胞在局部晚期鼻咽癌中的远期预后价值

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作者：邹弯弯南昌大学

学位级别：硕士

目的:鼻咽癌组织中存在着复杂的肿瘤微环境。随着对肿瘤微环境研究的深入,肿瘤微环境中的肿瘤相关巨噬细胞(Tumor-associated macrophages,TAMs)在肿瘤的发生发展中发挥着重要作用。TAMs可分为M1型巨噬细胞和M2型巨噬细胞;其中CD68是M1... 详细信息

目的:鼻咽癌组织中存在着复杂的肿瘤微环境。随着对肿瘤微环境研究的深入,肿瘤微环境中的肿瘤相关巨噬细胞(Tumor-associated macrophages,TAMs)在肿瘤的发生发展中发挥着重要作用。TAMs可分为M1型巨噬细胞和M2型巨噬细胞;其中CD68是M1型巨噬细胞和M2型巨噬细胞的相关抗原。CD163是M2型巨噬细胞特有的相关抗原。本研究通过CD163和CD68免疫组化双染在鼻咽癌的表达,分析不同分型的TAMs的浸润程度与临床特征之间的联系,并探讨不同分型TAMs浸润程度与鼻咽癌预后的相关性。方法:选取我院2014年至2017年239例鼻咽癌患者,组织病理类型为非角化性鳞状细胞癌;病理组织石蜡切片,通过CD163和CD68全自动免疫组化双染标记出三组肿瘤相关巨噬细胞;CD163+CD68+TAMs(M2)、CD163+CD68-TAMs以及CD163-CD68+TAMs;病理切片全景扫描;HALO数字病理图像分析,应用HALO数字病理图像分析软件对CD163表达、CD68表达、三组肿瘤相关巨噬细胞进行定量分析,得出阳性区域面积占比;根据DMFS随访数据采用X-tile分析软件得出最佳cut-off值;采用Kaplan-Meier法计算生存率,应用Log-rank分析不同因素对预后的影响,采用秩和检验和卡方检验分析CD68、CD163以及三组肿瘤相关巨噬细胞与临床特征的相关性,采用Spearman方法分析三组肿瘤巨噬细胞浸润程度的相关性,多因素分析采用Cox回归模型分析不同因素与鼻咽癌预后的相关性;数据分析采用IBM公司生产的统计学软件SPSS,版本为26.0。研究采用R语言C-Index方法比较CD163+CD68+TAMs与CD163+CD68-TAMs浸润程度在鼻咽癌预后价值(windows版本)。结果:1全组患者中位随访64个月,范围2-96个月。在随访过程中有27例(11.3%)患者死亡,18例(7.5%)出现复发,24例(10%)出现远处转移。5年总生存率87.2%,五年无进展生存率75.3%,5年无复发生存率90.5%,5年无远处转移生存率87.8%。2 Kaplan-Meier分析显示CD163+CD68+TAMs(M2)低浸润患者5年OS(93.6%vs.82.8%,P=0.001)、5年PFS(85%vs.60%,POS、PFS、DMFS的独立危险因素(P=0.012,P=0.002,P=0.005)。CD163+CD68-TAMs低浸润患者5年OS(90.5%vs.86.3%,P=0.024)、5年DMFS(91%vs.79.3%,P=0.017)高于高浸润患者。CD163-CD68+TAMs浸润程度与患者OS、PFS、RFS、DMFS均无相关性(P>0.05)。3卡方检验分析显示CD163+CD68+TAMs与CD163+CD68-TAMs的高浸润程度比例男性高于女性(P60岁患者高于年龄≤60岁(P60岁患者(P0.05)。4在临床特征与鼻咽癌预后的单因素分析中发现IV患者的OS显著劣于III期患者(HR=0.382,P=0.023);化疗周期数≥2的患者的RFS高于化疗周期数OS的独立影响因子(P=0.044),化疗周期不是患者RFS的独立影响因子(P=0.080)。年龄、性别、血浆EBDNA和LDH均不是患者预后影响因子。5研究采用C-Index得出CD163+CD68+TAMs浸润程度对预后评估性能优于CD163+CD68-TAMs。结论:CD163+CD68+TAMs(M2)浸润程度可以作为患者OS、PFS、DMFS的独立危险因素(P<0.05)。提示CD163+CD68+TAMs浸润程度是预测鼻咽癌总生存期、无进展生存期以及远处转移风险的指标。

关键词：鼻咽癌 CD68 CD163 M2型巨噬细胞肿瘤相关巨噬细胞(TAMs) OS PFS RFS DMFS

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Comparing overall survival between first generation EGFR-TKIs and chemotherapy in lung cancer patients with Del19/L858R

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Chinese Journal of Cancer Research 2016年第3期28卷 339-347页

作者： Wei Deng Yuanyuan Lei Siyang Liu Jinji Yang Haiyan Tu Honghong Yan Yilong Wu Second Clinical Medial Committee Southern Medical University Guangzhou 510515 China Guangdong Lung Cancer Institute Guangdong General Hospital and Guangdong Academy of Medical Sciences Guangzhou 510080 China

Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line second generation EGFR tyrOSine kinase inhibitors （TKIs） afatinib but not for thOSe with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups. Methods： Eligibles were all prOSpective and retrOSpective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratiOS （HRs）. All measures were pooled using random- effects models and 95% confidential interval （95% CI） was calculated. Results： A total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials （RCTs）, first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy （pooled HR_TKI/Chemo for Del19： 0.82, 95% CI： 0.64- 1.06, P=0.14; pooled HR_TKI/Chemo for L858R： 1.15, 95% CI： 0.85-1.56, P=0.38）. Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference （pooled HR19/21： 0.88, 95% CI： 0.67-1.16, P=0.37）. Conclusions： Among patients with advanced non-small cell hmg cancer （NSCLC） harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.

关键词： NSCLC EGFR Del19/L858R first generation EGFR-TKIs OS

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