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Resistance to chemoimmunotherapy in non-small-cell lung cancer

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Cancer Drug Resistance 2020年第3期3卷 445-453页

作者： maximilian Johannes hochmair Respiratory Oncology Unit Vienna North Hospital-Klinik FloridsdorfVienna 1210Austria.

Recent clinical trials evaluating the combination of chemotherapy with immune checkpoint inhibition for the primary treatment of lung cancer showed increased progression-free and overall survival compared with chemotherapy ***,the combination of these two modalities is less than additive and the mechanisms of resistance to this therapeutic intervention are discussed *** far,the conventional biomarkers for immunotherapy,namely programmed death-ligand 1 expression or tumor mutational burden are poor predictors of the efficacy of immunochemotherapy,and the optimal sequence of chemotherapy and immunotherapy has yet to be defined.

关键词： Lung cancer chemotherapy immunotherapy combination pembrolizumab resistance

Protection of small-cell lung cancer circulating tumor cells by cellular fragmentation

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Journal of Cancer Metastasis and Treatment 2020年第1期6卷 345-354页

作者： Barbara Rath Adelina Plangger Doris Moser maximilian hochmair Ernst Ulsperger Gerhard Hamilton Department of Vascular Surgery Medical University of ViennaVienna A-1190Austria Department of Cranio-Maxillofacial and Oral Surgery Medical University of ViennaVienna A-1090Austria Hospital Floridsdorf Vienna A-1210Austria Hospital Horn Horn A-3580Austria

Aim:Small-cell lung cancer(SCLC)disseminates aggressively and may exhibit high chemoresistance and poor survival *** this study,we aimed to investigate a new mechanism of drug resistance for SCLC circulating tumor cells(CTCs).Methods:SCLC CTC cell lines(n=4)which shed cellular fragments(MAT),as demonstrated by light and scanning electron microscopy,are compared to permanent SCLC *** proteins are detected by proteome arrays and the functional impact of MAT is studied using cytotoxicity tests involving cisplatin and ***:The SCLC CTC lines revealed layers of attached cellular fragments with a range of decreasing sizes from intact cells(approximately 12μm)down to small debris(approximately 2μm)which are not detectable in permanent SCLC *** SCLC CTC clusters represent cores of these fragment-coated *** profiling of MAT revealed a protein pattern similar to intact *** tests employing SCLC and SCLC CTC lines with chemotherapeutics used in therapy of SCLC demonstrated an inhibitory activity of MAT on the resulting ***:Generation of cell-associated debris by SCLC CTCs offers protective effects against cytotoxic drugs,representing a novel mechanism allowing survival of SCLC CTCs in patients.

关键词： Small cell lung cancer circulating tumor cells shedding topotecan

Analyzing the effect of earthquakes on OpenStreetMap contribution patterns and tweeting activities

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Geo-Spatial Information Science 2018年第3期21卷 195-212页

作者： Ahmed Ahmouda Hartwig H.hochmair Sreten Cvetojevic Geomatics Program Fort Lauderdale Research and Education CenterUniversity of FloridaFloridaFort LauderdaleUSA

Natural disasters,such as wildfires,earthquakes,landslides,or floods,lead to an increase in topical information shared on social media and in increased mapping activities in volunteered geographic information(VGI)*** earthquakes in Nepal and Central Italy as case studies,this research analyzes the effects of natural disasters on short-term(weeks)and longer-term(half year)changes in OpenStreetMap(OSM)mapping behavior and tweet activities in the affected *** increase of activities in OSM during the events can be partially attributed to those focused OSM mapping campaigns,for example,through the Humanitarian OSM Team(HOT).Using source tags in OSM change-sets,it was found that only a small portion of external mappers actually travels to the affected regions,whereas the majority of external mappers relies on desktop mapping ***,the study analyzes the spatio-temporal sequence of posted tweets together with keyword filters to identify a subset of users who most likely traveled to the affected regions for support and rescue *** also explores where,geographically,earthquake information spreads within social networks.

关键词： Volunteered geographic information(VGI) OpenStreetMap(OSM) Twitter natural disaster human dynamics

Where to catch'em all?-a geographic analysis of Pokémon Go locations

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Geo-Spatial Information Science 2017年第3期20卷 241-251页

作者： Levente Juhász Hartwig H.hochmair Geomatics Program University of FloridaFort LauderdaleFLUSA

In 2016,Niantic Labs released Pokémon Go,an augmented reality smartphone game that attracted millions of users *** game allows users to“catch”Pokémons through their mobile cameras in different geographic locations that often correspond to prominent *** paper analyzes the distribution of PokéStops,Pokémon gyms,and spawnpoints in selected urban areas of South Florida and *** identifies which socioeconomic variables and landuse categories affect the density of PokéStops,and how PokéStops and gyms cluster relative to each *** nearest neighbor analysis,this paper assesses also how actual PokéStop locations are reflected in Yelp’s“PokéStop nearby”*** show that black and Hispanic neighborhoods are disadvantaged when it comes to crowd-sourced data coverage,that PokéStops occur more frequently in commercial,recreational and touristic sites and around universities,and that PokéStops tend to cluster around *** latter suggests that these point sets were generated by a similar location selection *** mitigate geographically linked biases,future versions of augmented reality and geo-games should aim to make them equally accessible in all areas,for example by placing extra resources,such as points of interest,in neighborhoods that are currently underrepresented in data coverage.

关键词： Pokémon Go VGI(Volunteered Geographic Information) Yelp cluster South Florida Boston HCl(human-computer interaction)

Challenging aspects of contemporary cochlear implant electrode array design

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2017年第4期3卷 192-199页

作者： Pavel Mistrík Claude Jolly Daniel Sieber Ingeborg hochmair MED-EL Company Austria

Objective:A design comparison of current perimodiolar and lateral wall electrode arrays of the cochlear implant (CI) is *** focus is on functional features such as acoustic frequency coverage and tonotopic mapping,battery consumption and dynamic range.A traumacity of their insertion is also ***:Review of up-to-date ***:Perimodiolar electrode arrays are positioned in the basal turn of the cochlea near the *** are designed to initiate the action potential in the proximity to the neural soma located in spiral *** the other hand,lateral wall electrode arrays can be inserted deeper inside the cochlea,as they are located along the lateral wall and such insertion trajectory is less *** class of arrays targets primarily surviving neural peripheral *** to their larger insertion depth,lateral wall arrays can deliver lower acoustic frequencies in manner better corresponding to cochlear *** fact,spiral ganglion sections containing auditory nerve fibres tuned to low acoustic frequencies are located deeper than 1 and half turn inside the *** this reason,a significant frequency mismatch might be occurring for apical electrodes in perimodiolar arrays,detrimental to speech *** languages such as Mandarin might be therefore better treated with lateral wall *** the other hand,closer proximity to target tissue results in lower psychophysical threshold levels for perimodiolar ***,the maximal comfort level is also lower,paradoxically resulting in narrower dynamic range than that of lateral wall *** consumption is comparable for both types of ***:Lateral wall arrays are Less likely to cause trauma to cochlear *** the current trend in cochlear implantation is the maximal protection of residual acoustic hearing,the Lateral wall arrays seem more suitable for hearing preservation Cl *** development could focus on combini

关键词： Cochlear implant

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人工耳蜗四年经验小结

国际生物医学工程杂志 1982年第4期 251-257页

作者： I.J.hochmair-Desoyer 林金森

一、引言 1957年已经提出了用人工耳蜗使全聋病人重新听到声音的想法,当时DjournO等人第一次把电极植入到听神经附近,并且通过电刺激这些神经使其诱发出类似于噪声的感觉。在正常的耳朵中,传来的声波引起鼓膜的振动。这个振动通过中耳... 详细信息

一、引言 1957年已经提出了用人工耳蜗使全聋病人重新听到声音的想法,当时DjournO等人第一次把电极植入到听神经附近,并且通过电刺激这些神经使其诱发出类似于噪声的感觉。在正常的耳朵中,传来的声波引起鼓膜的振动。这个振动通过中耳内的三个小骨传导到卵圆窗膜,并且激发耳蜗内的外淋巴液的运动。耳蜗包括三个充满液体的阶,根据传来的声音的频率,内耳的液体在沿着耳蜗长度的特定部位、呈现出最大的运动。克氏器

关键词：人工耳蜗全聋病人鼓阶圆窗蜗窗

培美曲塞加铂类联合或不联合帕博利珠单抗对初治转移性非鳞状NSCLC患者的疗效与安全性分析：KEYNOTE-189研究方案指定的最终分析

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中国肺癌杂志 2022年第6期25卷 443-456页

作者：周彩存 Delvys RODRíGUEZ-ABREU S.F.POWELL M.J.hochmair S.GAD GEEL E.ESTEBAN E.FELIP G.SPERANZA F.De ANGELIS M.DóMINE S.Y.CHENG H.G.BISCHOFF N.PELED M.RECK R.HUI E.B.GARON M.BOYER T.KURATA J.YANG M.C.PIETANZA F.SOUZA M.C.GARASSINO Thoraxklinik Heidelberg LungenClinic Airway Research Center NorthGerman Center for Lung Research Department of Medical Oncology Chris O'Brien Lifehouse Fondazione IRCCS Istituto Nazionale dei Tumori Medical Oncology Department Vall d'Hebron UniversityVall d'Hebron Institute of Oncology (VHIO) 8. Centre Integre de Cancerologie de la MontérégieH?pital Charles-Le Moyne 9. Medical Oncology DepartmentHospital Universitario Fundacidn Jiménez DiazIIS-FJD Oncology Sanford Health 4. Department of Respiratory and Critical Care MedicineKarl Landsteiner Institute of Lung Research and Pulmonary Oncology Department of Thoracic Oncology Kansai Medical University Hospital Merck & Co. Inc. University of Chicago Medicine & Biological Sciences Knapp Center for Biomedical Discovery Department of Medical Oncology Hospital Universitario Central de Asturias Medical Oncology Complejo Hospitalario Universitario Insular Materno-Infantil de Gran CanariaUniversidad de Las Palmas de Gran Canaria Department of Oncology Shaare Zedek Medical Center Department of Medical Oncology Westmead Hospital and University of Sydney Department of Medicine David Geffen School of Medicine at UCLA 同济大学附属上海市肺科医院肿瘤科 Sunnybrook Health Sciences Centre Thoracic Oncology Karmanos Cancer InstituteWayne State University

背景在KEYNOTE-189此项Ⅲ期研究(NCT02578680)中,与安慰剂联合培美曲塞加铂类相比,帕博利珠单抗联合培美曲塞加铂类化疗(培美曲塞-铂类)显著改善了初治转移性非鳞状非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的总生存期(over... 详细信息

背景在KEYNOTE-189此项Ⅲ期研究(NCT02578680)中,与安慰剂联合培美曲塞加铂类相比,帕博利珠单抗联合培美曲塞加铂类化疗(培美曲塞-铂类)显著改善了初治转移性非鳞状非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的总生存期(overall survival,OS)和无进展生存期(progression-free survival,PFS)。本研究报告了研究方案指定的最终分析的疗效结局,包括从培美曲塞-铂类交叉至帕博利珠单抗治疗的患者,以及完成35个周期(约2年)帕博利珠单抗治疗组的疗效。方法符合条件的患者以2:1随机分配至帕博利珠单抗,每3周一次,200 mg (n=410)或安慰剂(n=206)(共35周期,约2年),加上4个周期的培美曲塞(500 mg/m~2)和由研究者选择的每3周顺铂(75 mg/m~2)或卡铂(曲线下面积5 mg/min/mL)治疗,随后使用培美曲塞直至疾病进展。若符合纳入标准,分配至安慰剂联合培美曲塞加铂类治疗的患者可在疾病进展时转向帕博利珠单抗治疗。主要研究终点为OS和PFS。结果中位随访31.0个月,无论PD-L1的表达水平如何,与安慰剂联合培美曲塞-铂类治疗相比,帕博利珠单抗联合培美曲塞-铂类治疗可使患者的OS[风险比(hazard ratio,HR)为0.56;95%可信区间(confidence interval,CI) 0.46-0.69]和PFS (HR=0.49;95%CI:0.41-0.59)显著获益。接受帕博利珠单抗联合培美曲塞-铂类治疗的患者客观缓解率(objective response rate,ORR)(48.3%vs 19.9%)和第二次/后续无进展生存期(PFS2;HR=0.50;95%CI:0.41-0.61)均得到改善。安慰剂联合培美曲塞-铂类组的84例患者(40.8%)交叉至帕博利珠单抗治疗组。72.1%的接受帕博利珠单抗联合培美曲塞-铂类的患者和66.8%的接受安慰剂联合培美曲塞-铂类的患者发生了3级-5级不良事件。56例患者完成了35个周期(约2年)的帕博利珠单抗治疗;ORR为85.7%,53例(94.6%)患者存活至数据截止时间。结论与安慰剂联合培美曲塞-铂类治疗相比,帕博利珠单抗联合培美曲塞-铂类可持续提高疗效,且安全性可控。该研究结果支持将帕博利珠单抗联合培美曲塞-铂类作为初治转移性非鳞状NSCLC患者的一线治疗方案。

关键词：帕博利珠单抗化疗非鳞状非小细胞肺癌