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驱动基因阴性的转移性非小细胞肺癌最佳免疫治疗方案的选择

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中国肺癌杂志 2022年第7期25卷 555-582页

作者： Michael J.GRANT roy s.herbst sarah B.GOLDBERG 刘明 Department of Medicine (Medical Oncology) Yale School of MediineYale Cancer Center 广州医科大学附属第一医院呼吸科国家呼吸医学中心

驱动基因阴性的非小细胞肺癌(non-small celllung cancer,NsCLC)治疗策略进展迅速。其中,免疫检查点抑制剂,特别是针对程序性死亡受体1 (programmed death 1,PD-1)/程序性死亡配体1 (programmed death-ligand 1,PD-L1)的免疫检查点抑制...

驱动基因阴性的非小细胞肺癌(non-small celllung cancer,NsCLC)治疗策略进展迅速。其中,免疫检查点抑制剂,特别是针对程序性死亡受体1 (programmed death 1,PD-1)/程序性死亡配体1 (programmed death-ligand 1,PD-L1)的免疫检查点抑制剂,已在部分NsCLC患者中显示出持久疗效,成为驱动基因阴性NsCLC一线治疗的基石。对于初治患者,目前获批的免疫治疗策略包括免疫单药治疗、免疫联合免疫方案或免疫治疗联合化疗。尽管几项重要临床研究中的长期疗效和安全性数据可以为不同患者亚群的最佳治疗选择提供见解,但鉴于缺乏头对头的前瞻性研究,不同患者亚群的治疗决策仍然十分复杂。事实上,尽管组织学亚型和肿瘤细胞PD-L1表达水平对治疗方案的选择尤为重要,但某些情况下其他临床病理因素和患者意愿也可能影响治疗方案的选择。目前针对新型生物标志物和治疗新策略的研究正在开展,有望进一步完善当前的治疗模式。该综述讨论了现有治疗方案,并详细介绍了驱动基因阴性的晚期NsCLC患者的一线免疫治疗方案的选择。

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帕博利珠单抗单药治疗PD-L1阳性伴脑转移的非小细胞肺癌患者的疗效：KEYNOTE-001、010、024和042研究的汇总分析

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中国肺癌杂志 2022年第9期25卷 701-712页

作者： Aaron s. MANsFIELD roy s. herbst Gilberto de CAsTRO Jr. Rina HUI Nir PELED Dong-Wan KIM silvia NOVELLO Miyako sATOUCHI Yi-Long WU Edward B.GARON Martin RECK Andrew G.ROBINsON Ayman sAMKaRI Bilal PIPERDI Victoria EBIANA Jianxin LIN Tony s.K.MOK 黎扬斯 David Geffen school of Medicine at the University of California Los Angeles Lung Clinic Grosshansdorf Airway Research Center North German Center of Lung Research Cancer Centre of southeastern Ontario at Kingston General Hospital Merck & Co. Inc. state Key Laboratory of Translational Oncology Chinese University of Hong Kong 广东省人民医院广东省人民医院肿瘤医院广东省肺癌研究所 Division of Medical Oncology Mayo Clinic Yale Comprehensive Cancer Center Yale University School of Medicine Instituto do Cancer do Estado de s?o Paulo Westmead Hospital and the University of sydney soroka Cancer Center Ben Gurion University seoul National University Hospital Seoul National University College of Medicine Azienda Ospedaliero-Universitaria san Luigi Gonzaga University of Turin Hyogo Cancer Center Guangdong Lung Cancer Institute Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences

背景与目的我们回顾性评估了程序性死亡配体1（programmed death ligand 1, PD-L1）阳性非小细胞肺癌（non-small cell lung cancer, NsCLC）患者的预后，以比较基线（即入组时）脑转移与帕博利珠单抗及化疗的疗效关系。方法我们汇总... 详细信息

背景与目的我们回顾性评估了程序性死亡配体1（programmed death ligand 1, PD-L1）阳性非小细胞肺癌（non-small cell lung cancer, NsCLC）患者的预后，以比较基线（即入组时）脑转移与帕博利珠单抗及化疗的疗效关系。方法我们汇总分析了KEYNOTE-001（NCT01295827）、KEYNOTE-010（NCT01905657）、KEYNOTE-024（NCT02142738）和KEYNOTE-042（NCT02220894）研究中既往接受过治疗或未接受过的PD-L1阳性[肿瘤细胞阳性比例评分（tumor proportion score, TPs）≥1%]的晚期或转移性NsCLC患者的数据。患者接受帕博利珠单抗（2 mg/kg,10 mg/kg，或每3周200 mg或每2周10 mg/kg）治疗；而化疗是除KEYNOTE-001外所有研究的对照组。所有研究都纳入了既往接受过治疗的稳定脑转移的患者。结果共计纳入3,170例患者，基线时，293例（9.2%）患者伴有脑转移，而2,877例（90.8%）是无脑转移患者；数据截止时，中位（范围）随访时间为12.9（0.1-43.7）个月。与化疗相比，帕博利珠单抗可改善基线伴有脑转移及无脑转移患者的总生存期：PD-L1 TPs≥50%[分别为0.67（95%CI:0.44-1.02）和0.66（95%CI:0.58-0.76）]和PD-L1 TPs≥1%[分别为0.83（95%CI:0.62-1.10）和0.78（95%CI:0.71-0.85）]。无论是否有脑转移，与化疗相比，接受帕博利珠单抗治疗患者的无进展生存期更长，客观缓解率更高，缓解持续时间更长。在脑转移患者中，帕博利珠单抗与化疗的治疗相关不良事件发生率分别为66.3%和84.4%，在无脑转移患者中分别为67.2%和88.3%。结论对于既往未接受治疗或接受过治疗的PD-L1阳性晚期/转移性NsCLC患者，无论基线时是否存在治疗后稳定的脑转移，帕博利珠单抗单药治疗显示出明显的疗效改善，且与化疗相比，不良事件更少。

关键词：帕博利珠单抗脑转移化疗非小细胞肺癌 PD-L1

Mechanism of Cu entry into the brain:many unanswered questions

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Neural Regeneration Research 2024年第11期19卷 2421-2429页

作者： shubhrajit roy svetlana Lutsenko Department of Physiology Johns Hopkins University School of MedicineBaltimoreMDUSA

Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavenging.The requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional status.Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and others.Despite the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well defined.This review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.

关键词： ATOX1 ATP7A ATP7B blood-brain barrier brain choroid plexus copper sLC31A1

帕博利珠单抗治疗伴脑转移NsCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析

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中国肺癌杂志 2021年第9期24卷 I0007-I0016页

作者： sarah B GOLDBERG Kurt A sCHALPER scott N GETTINGER Amit MAHAJAN roy s herbst Anne C CHANG Rogerio LILENBAUM Frederick H WILsON sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRsH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) Department of Medicine(Medical Oncology) Yale School of MedicineNew HavenCTUSA Department of Pathology Yale School of MedicineNew HavenCTUSA Department of Radiology Yale School of MedicineNew HavenCTUSA Department of Neurosurgery Yale School of MedicineNew HavenCTUSA Department of Therapeutic Radiology Yale School of MedicineNew HavenCTUSA Interdepartmental Program in Computational Biology and Bioinformatics Yale School of MedicineNew HavenCTUSA Department of Biostatistics Yale School of Public HealthNew HavenCTUSA 华中科技大学同济医学院附属协和医院胸部肿瘤科

背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NsCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(ce... 详细信息

背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NsCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNs)中的疗效。中期结果已发表,现报道对NsCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NsCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)s.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NsCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NsCLC合并CNs转移。

关键词：非小细胞肺癌脑转移免疫治疗帕博利珠单抗

Association between people’s attitudes towards human-elephant conflict and their locational,demographic,and socio-economic characteristics in Buxa Tiger Reserve and its adjoining area,India

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Regional sustainability 2024年第1期5卷 11-25页

作者： Chiranjib NAD Tamal BAsU-roy Department of Geography Raiganj UniversityRaiganj733134India

“Human-elephant conflict(HEC)”,the alarming issue,in present day context has attracted the attention of environmentalists and policy makers.The rising conflict between human beings and wild elephants is common in Buxa Tiger Reserve(BTR)and its adjoining area in West Bengal state,India,making the area volatile.People’s attitudes towards elephant conservation activity are very crucial to get rid of HEC,because people’s proximity with wild elephants’habitat can trigger the occurrence of HEC.The aim of this study is to conduct an in-depth investigation about the association of people’s attitudes towards HEC with their locational,demographic,and socio-economic characteristics in BTR and its adjoining area by using Pearson’s bivariate chi-square test and binary logistic regression analysis.BTR is one of the constituent parts of Eastern Doors Elephant Reserve(EDER).We interviewed 500 respondents to understand their perceptions to HEC and investigated their locational,demographic,and socio-economic characteristics including location of village,gender,age,ethnicity,religion,caste,poverty level,education level,primary occupation,secondary occupation,household type,and source of firewood.The results indicate that respondents who are living in enclave forest villages(EFVs),peripheral forest villages(PFVs),corridor village(CVs),or forest and corridor villages(FCVs),mainly males,at the age of 18–48 years old,engaged with agriculture occupation,and living in kancha and mixed houses,have more likelihood to witness HEC.Besides,respondents who are illiterate or at primary education level are more likely to regard elephant as a main problematic animal around their villages and refuse to participate in elephant conservation activity.For the sake of a sustainable environment for both human beings and wildlife,people’s attitudes towards elephants must be friendly in a more prudent way,so that the two communities can live in harmony.

关键词： Human-elephant conflict Elephant conservation Chi-square test statistics Binary logistic regression Demographic and socioeconomic characteristics Buxa Tiger Reserve

A hierarchical clustering approach for colorectal cancer molecular subtypes identification from gene expression data

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Intelligent Medicine 2024年第1期4卷 43-51页

作者： shivangi Raghav Aastha suri Deepika Kumar Aakansha Aakansha Muskan Rathore sudipta roy Department of Computer science&Engineering Bharati Vidyapeeth’s College of EngineeringNew DelhiIndia Artificial Intelligence&Data science Jio InstituteNavi Mumbai410206India

Background Colorectal cancer(CRC)is the second leading cause of cancer fatalities and the third most common human disease.Identifying molecular subgroups of CRC and treating patients accordingly could result in better therapeutic success compared with treating all CRC patients similarly.studies have highlighted the significance of CRC as a major cause of mortality worldwide and the potential benefits of identifying molecular subtypes to tailor treatment strategies and improve patient outcomes.Methods This study proposed an unsupervised learning approach using hierarchical clustering and feature selection to identify molecular subtypes and compares its performance with that of conventional methods.The proposed model contained gene expression data from CRC patients obtained from Kaggle and used dimension reduction techniques followed by Z-score-based outlier removal.Agglomerative hierarchy clustering was used to identify molecular subtypes,with a P-value-based approach for feature selection.The performance of the model was evaluated using various classifiers including multilayer perceptron(MLP).Results The proposed methodology outperformed conventional methods,with the MLP classifier achieving the highest accuracy of 89%after feature selection.The model successfully identified molecular subtypes of CRC and differentiated between different subtypes based on their gene expression profiles.Conclusion This method could aid in developing tailored therapeutic strategies for CRC patients,although there is a need for further validation and evaluation of its clinical significance.

关键词： Machine learning Colorectal cancer Feature selection Classification Clustering

晚期非小细胞肺癌治疗策略的演变：从2009放眼2012

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中国肺癌杂志 2010年第3期13卷 238-241页

作者： David R. GANDARA Philip C. MACK Tianhong LI Primo N. LARA JR roy s. herbst 杨永波(翻译) 周清华(校对) Division of Hematology and Oncology University of California Davis Cancer Center Sacramento CA Department of Oncology Montefiore-Einstein Cancer Center Bronx NY Department of Thoracic Head and Neck Medical Oncology University of TexasM. D. Anderson Cancer Center Houston TX 天津医科大学总医院天津市肺癌研究所天津市肺癌转移与肿瘤微环境重点实验室

新近的临床试验资料,包括2009年美国临床肿瘤协会（AsCO）年会上报道的资料,有力地推动了对晚期非小细胞肺癌（NsCLC）患者的现代治疗策略的改革。此改革蕴含的主题包括：（1）基于组织学类型的治疗,

关键词：晚期非小细胞肺癌现代治疗演变 2009年组织学类型试验资料肿瘤协会临床

Cellular interplay to 3D in vitro microphysiological disease model:cell patterning microbiota-gut-brain axis

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Bio-Design and Manufacturing 2024年第3期7卷 320-357页

作者： Kamare Alam Lakshmi Nair souvik Mukherjee Kulwinder Kaur Manjari singh santanu Kaity Velayutham Ravichandiran sugato Banerjee subhadeep roy Department of Pharmacology and Toxicology National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India Department of Pharmaceutical sciences Assam UniversitySilchar 788011India Department of Pharmaceutical sciences Guru Ghasidas UniversityKoniBilaspur 495009C.G.India school of Pharmacy and Biomolecular sciences RCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Tissue Engineering Research Group Department of Anatomy and Regenerative MedicineRCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Department of Pharmaceutics National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India Department of Natural Products National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India

The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the gut.Homeostasis between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological conditions.The most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune cells.However,each pathway is intertwined with a complex one.With the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative diseases.This paper briefly retraces the possible communication pathways between the gut microbiome and the brain.It further elaborates on three major diseases:autism spectrum disorder,Parkinson’s disease,and Alzheimer’s disease,which are prevalent in children and the elderly.These diseases also decrease patients’quality of life.Hence,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the diseases.Remodeling of MGBA in the laboratory uses many molecular technologies and biomaterial advances.spheroids and organoids provide a more realistic picture of the cell and tissue structure than monolayers.Combining them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between them.Cutting-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.

关键词： Microbiota-gut-brain axis Neurodegeneration 3D disease model Organoid Transwell system

Exploring the effects of dietary inulin in rainbow trout fed a high‑starch,100%plant‑based diet

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Journal of Animal science and Biotechnology 2024年第2期15卷 713-732页

作者： Raphaël Defaix Jep Lokesh Laura Frohn Mickael Le Bechec Thierry Pigot Vincent Veron Anne surget sandra Biasutti Frederic Terrier sandrine skiba-Cassy Jerome roy stephane Panserat Karine Ricaud Universite de Pau Et Des Pays de L’Adour E2S UPPAINRAENUMEASaint‑Pee‑Sur‑NivelleFrance Universite de Pau Et Des Pays de L’Adour E2S UPPACNRSIMT Mines AlesIPREMPauFrance Universite de Pau Et Des Pays de L’Adour E2S UPPAIUT des Pays de l’AdourDepartement Genie BiologiqueMont de MarsanFrance.

Background High dietary carbohydrates can spare protein in rainbow trout(Oncorhynchus mykiss)but may affect growth and health.Inulin,a prebiotic,could have nutritional and metabolic effects,along with anti-inflammatory properties in teleosts,improving growth and welfare.We tested this hypothesis in rainbow trout by feeding them a 100%plant-based diet,which is a viable alternative to fishmeal and fish oil in aquaculture feeds.In a two-factor design,we examined the impact of inulin(2%)as well as the variation in the carbohydrates(CHO)/plant protein ratio on rainbow trout.We assessed the influence of these factors on zootechnical parameters,plasma metabolites,gut microbiota,production of short-chain fatty acids and lactic acid,as well as the expression of free-fatty acid receptor genes in the mid-intestine,intermediary liver metabolism,and immune markers in a 12-week feeding trial.Results The use of 2%inulin did not significantly change the fish intestinal microbiota,but interestingly,the high CHO/protein ratio group showed a change in intestinal microbiota and in particular the beta diversity,with 21 bacterial genera affected,including Ralstonia,Bacillus,and 11 lactic-acid producing bacteria.There were higher levels of butyric,and valeric acid in groups fed with high CHO/protein diet but not with inulin.The high CHO/protein group showed a decrease in the expression of pro-inflammatory cytokines(il1b,il8,and tnfa)in liver and a lower expression of the genes coding for tight-junction proteins in mid-intestine(tjp1a and tjp3).However,the 2%inulin did not modify the expression of plasma immune markers.Finally,inulin induced a negative effect on rainbow trout growth performance irrespective of the dietary carbohydrates.Conclusions With a 100%plant-based diet,inclusion of high levels of carbohydrates could be a promising way for fish nutrition in aquaculture through a protein sparing effect whereas the supplementation of 2%inulin does not appear to improve the use of CHO when combined with a 100%plant-based diet.

关键词： Aquaculture Fish nutrition Gut microbiota Immune markers Intermediary metabolism Inulin Prebiotic Rainbow trout short-chain fatty acids