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靶向DLL3的双特异性抗体和CAR-T用于小细胞肺癌的免疫治疗研究

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靶向DLL3的双特异性抗体和CAR-T用于小细胞肺癌的免疫治疗研究

作者： NORHAN mohamed HAMDY emam AMAR 华中农业大学

学位级别：硕士

小细胞肺癌(SCLC)在肺癌患者约占15%,通常与吸烟有密切关系,小细胞肺癌被归类为侵略性程度非常高的肺癌。SCLC的治疗方法首先从化学疗法和放射疗法开始。由于SCLC通常分为局限性(LD)和广泛性(ED)两个阶段,SCLC的患者中有70%被诊断为广... 详细信息

小细胞肺癌(SCLC)在肺癌患者约占15%,通常与吸烟有密切关系,小细胞肺癌被归类为侵略性程度非常高的肺癌。SCLC的治疗方法首先从化学疗法和放射疗法开始。由于SCLC通常分为局限性(LD)和广泛性(ED)两个阶段,SCLC的患者中有70%被诊断为广泛阶段。DLL3被认为是SCLC免疫疗法的理想靶标,因为它在SCLC患者中高表达,而在正常组织中几乎不表达。免疫检查点抑制剂和DLL3靶向抗体偶联药物是目前SCLC免疫疗法中研究比较多的免疫治疗方法。双特异性抗体是通过将T细胞和肿瘤细胞直接桥连起来从而发挥T细胞的肿瘤杀伤活性。CAR-T细胞是将抗体片段表达在T细胞的表面,提高了T细胞对肿瘤细胞的识别与杀伤活性。本论文构建了靶向DLL3的双特异性抗体和CAR-T,并研究了它们对小细胞肺癌的杀伤活性。双特异性抗体的构建采用经典的knob-into-hole结构,其中靶向DLL3的抗体片段SC16.15与h Fc(knob)融合,靶向CD3的抗体片段OKT3与h Fc(hole)融合。CART细胞构建采用第三代结构,由抗体片段SC16.15、CD8跨膜区、共激活域CD28、4-1BB和CD3z构成。DLL3双特异性抗体和CAR-T的肿瘤杀伤活性均通过细胞水平和和体内移植瘤小鼠模型测试。双特异性抗体的细胞结合活性分别用DLL3阴性的A431细胞和DLL3阳性的小细胞肺癌细胞系、T淋巴瘤细胞系Jurkat和原代PBMC细胞进行测试。双特异性抗体和CAR-T的肿瘤杀伤活性通过荧光素酶法进行测试,首先用慢病毒载体将荧光素酶报告基因导入上述细胞系中,通过测试荧光素酶活性的下降确定双特异性抗体和CAR-T的体外杀伤活性。双特异性抗体和CAR-T的体内抑瘤活性在NSG小鼠中测试,通过向NSG小鼠皮下接种SCLC细胞,待成瘤后,通过腹腔注射PBMC细胞和尾静脉注射双特异性抗体,或腹腔注射CAR-T细胞,观察对肿瘤生长的抑制作用。体外杀伤结果显示,靶向DLL3的双特异性抗体和CAR-T均可迅速杀死DLL3阳性的小细胞肺癌细胞系H446,H196,H82,和超表达DLL3的A431细胞系系。体内抑瘤活性试验显示,双特异性抗体和CAR-T对肿瘤的生长均具有明显的抑制作用。联合PD-1检查点抑制抗体可以提高DLL3双特异性抗体的抑瘤活性,但未能加强CAR-T的抗肿瘤活性。总体来说,本研究的结果表明,以DLL3为靶点的双特异性抗体和CAR-T对小细胞肺癌均有很强的抑瘤活性,其中,DLL3双特异抗体联合PD-1抗体对SCLC的抑瘤效果更理想。

关键词：小细胞肺癌 DLL3 双特异性抗体 CAR-T PD-1抗体

An Enhanced Lung Cancer Detection Approach Using Dual-Model Deep Learning Technique

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 835-867页

作者： Sumaia mohamed Elhassan Saad mohamed Darwish Saleh Mesbah Elkaffas Department of Information Technology Institute of Graduate Studies and ResearchAlexandria UniversityAlexandria21526Egypt College of Computing and Information Technology Arab Academy for ScienceTechnology and Maritime TransportAlexandriaP.O.Box 1029Egypt

Lung cancer continues to be a leading cause of cancer-related deaths worldwide,emphasizing the critical need for improved diagnostic *** detection of lung tumors significantly increases the chances of successful treatment and ***,current diagnostic methods often fail to detect tumors at an early stage or to accurately pinpoint their location within the lung ***-model deep learning technologies for lung cancer detection,while beneficial,cannot capture the full range of features present in medical imaging data,leading to incomplete or inaccurate ***,it may not be robust enough to handle the wide variability in medical images due to different imaging conditions,patient anatomy,and tumor *** overcome these disadvantages,dual-model or multi-model approaches can be *** research focuses on enhancing the detection of lung cancer by utilizing a combination of two learning models:a Convolutional Neural Network(CNN)for categorization and the You Only Look Once(YOLOv8)architecture for real-time identification and pinpointing of *** automatically learn to extract hierarchical features from raw image data,capturing patterns such as edges,textures,and complex structures that are crucial for identifying lung ***8 incorporates multiscale feature extraction,enabling the detection of tumors of varying sizes and scales within a single *** is particularly beneficial for identifying small or irregularly shaped tumors that may be challenging to ***,through the utilization of cutting-edge data augmentation methods,such as Deep Convolutional Generative Adversarial Networks(DCGAN),the suggested approach can handle the issue of limited data and boost the models’ability to learn from diverse and comprehensive *** combined method not only improved accuracy and localization but also ensured efficient real-time processing,which is crucial for practical clinical applicati

关键词： Lung cancer detection dual-model deep learning technique data augmentation CNN YOLOv8

Molluscicidal effectiveness of Luo-Wei,a novel plant-derived molluscicide,against Oncomelania hupensis,Biomphalaria alexandrina and Bulinus truncatus

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Infectious Diseases of Poverty 2019年第2期8卷 70-79页

作者： Tie-Wu Jia Wei Wang Le-Ping Sun Shan Lv Kun Yang Neng-Min Zhang Xi-Bao Huang Jian-Bing Liu Han-Cheng Liu Rui-Hua Liu Fathia A.Gawish mohamed R.Habib mohamed A.El-emam Charles H.King Xiao-Nong Zhou National Institute of Parasitic Diseases Chinese Center for Disease Control and PreventionShanghai 200025China Chinese Center for Tropical Diseases Research Shanghai 200025China WHO Collaborating Centre for Tropical Diseases Shanghai 200025China National Center for International Research on Tropical Diseases Ministry of Science and TechnologyShanghai 200025China Key Laboratory of Parasite and Vector Biology Ministry of HealthShanghai 200025China Communicable Diseases Cluster World Health Organization Regional Office for Africa(WHO/AFRO)PO Box 06BrazzavilleCongo Key Laboratory of National Health Commission on Parasitic Disease Control and Prevention Jiangsu Provincial Key Laboratory on Parasites and Vector Control TechnologyJiangsu Institute of Parasitic DiseasesWuxi 214064China Hubei Jinhaichao Science&Technology Co. LtdWuhan 430206China Hubei Provincial Center for Disease Control and Prevention Wuhan 430079China School of Chemistry and Chemical Engineering Wuhan Textile UniversityWuhan 430200China Department of Medical Malacology Theodor Bilharz Research Institute(TBRI)ImbabaGiza 12411Egypt Center for Global Health and Diseases Case Western Reserve UniversityClevelandOHUSA Schistosomiasis Consortium for Operational Research and Evaluation University of GeorgiaAthensGAUSA

Background:Control of snail intermediate hosts has been proved to be a fast and efficient approach for interrupting the transmission of *** plant extracts have shown obvious molluscicidal activity,and a new compound Luo-Wei,also named tea-seed distilled saponin(TDS),was developed based on the saponins extracted from Camellia oleifera *** aimed to test the molluscicidal activity of 4%TDS against the intermediate host snails in China and Egypt,and evaluate its environmental safety to non-target ***:In the laboratory,Oncomelania hupensis,Biomphalaria alexandrina and Bulinus truncatus were exposed to 4%TDS,and the median lethal concentration(LC5o)was estimated at 24,48 and 72 *** the field,snail mortalities were assessed 1,2,3 and 7 d post-immersion with 2.5 g/m34%TDS and 1,3,7 and 15 d post-spraying with 5 g/m24%*** addition,the acute toxicity of 4%TDS to Japanese quail(Coturnixjaponica),zebrafish(Brachydanio rerio)and freshwater shrimp(Macrobrachium nipponense)was assessed by estimations of LC5o or median lethal dose(LD5o).Results:In the laboratory,the LC5o values of 4%TDS for *** were 0.701,0.371 and 0.33 mg/L at 24,48 and 72 h,respectively,and 4%TDS showed a 0.33 mg/L 24 h LC5o against ***,and a 1.396 mg/L 24 h LCs0 against *** all study regions,the pooled mortalities of *** were 72,86,94 and 98%at 1,2,3 and 7 d,following field immersion of 4%TDS at a dose of 2.5 g/m3,and were 69,77,85 and 88%at 1,3,7 and 15 d,following field spraying at 5 g/m2,respectively.4%TDS had moderate toxicity to Japanese quail(7 d LD5o>60 mg/kg)and to shrimp(96 h LCs0=6.28 mg/L;95%CI:3.53-11.2 mg/L),whereas its toxicity to zebrafish was high(96 h LCso--0.15 mg/L;95%CI:0.14-0.17 mg/L).Conclusions:4%TDS is active against ***,*** and *** under laboratory and field conditions,and it may be a candidate molluscicide of plant origin.

关键词： Schistosomiasis Luo-Wei Plant-derived molluscicide Oncomelania hupensis Biomphalaria alexandrina Bulinus truncatus Molluscicidal activity

Thermal effects on wear behavior of additively manufactured NiTi shape memory alloys

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Chinese Journal of Aeronautics 2025年第1期38卷 147-164页

作者： Xianghui HUANG Nan KANG Pei WANG mohamed EL MANSORI Arts et Metiers Institute of Technology MSMPHESAM UniversitéChâlons-en-Champagne 51006France Henan Key Laboratory of High-Performance Carbon Fiber Reinforced Composites Institute of Carbon Matrix CompositesHenan Academy of SciencesZhengzhou 450046China Texas A&M Engineering Experiment Station Institute for Manufacturing SystemsCollege StationTX 77843USA

NiTi alloys fabricated by laser powder bed fusion(LPBF)additive manufacturing technology not only address the compositional instability resulting from complex processes but also solve the challenges of difficult machining of intricate aerospace ***,there are very few reports on the wear behavior of LPBF-NiTi *** the present work,the effects of microstructure and thermal treatment,including heat treatment and frictional heat,on the wear behavior of LPBF-NiTi alloy and 100Cr6 ball were analyzed through a series of tribological experiments with different sliding *** the average sliding speed increases(0.079–0.216 m/s),the wear rate of the as-built and heat-treated samples tends to decrease in the range of 2.69×10^(-3)–0.97×10^(-3)mm^(3)/*** the heat-treated LPBF-NiTi alloy is 46%harder than the as-built alloy is,the latter has a higher toughness(505 MJ/m^(3))and greater transformation strain of SIM(0.097).This leads to a coupling effect of heat treatment and sliding speed on the wear *** addition,the wear track morphologies under different sliding speeds are asymmetric due to the 24% greater acceleration at the far end from the motor and the 2.15 mm deviation between the maximum speed position and the geometric center of the *** wear modes of the as-built and heat-treated samples included adhesive,abrasive and delamination ***,the wear morphologies and dominant wear modes change with the frictionally caused heat release induced by the sliding speed.

关键词： Additive manufacturing Laser powder bed fusion NiTi alloys Wear resistance Sliding speed

Feature selection strategy optimization for lithium-ion battery state of health estimation under impedance uncertainties

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Journal of Energy Chemistry 2025年第2期101卷 87-98页

作者： Xinghao Du Jinhao Meng Yassine Amirat Fei Gao mohamed Benbouzid UMR CNRS 6027 IRDL University of Brest School of Electrical Engineering Xi'an Jiaotong University LbISEN ISEN Yncréa Ouest School of Energy and Computer Science University of Technology of Belfort-Montbeliard

Battery health evaluation and management are vital for the long-term reliability and optimal performance of lithium-ion batteries in electric *** impedance spectroscopy(EIS) offers valuable insights into battery degradation analysis and ***,previous studies have not adequately addressed the impedance uncertainties,particularly during battery operating conditions,which can substantially impact the robustness and accuracy of state of health(SOH) *** by this,this paper proposes a comprehensive feature optimization scheme that integrates impedance validity assessment with correlation *** utilizing metrics such as impedance residuals and correlation coefficients,the proposed method effectively filters out invalid and insignificant impedance data,thereby enhancing the reliability of the input ***,the extreme gradient boosting(XGBoost) modeling framework is constructed for estimating the battery degradation *** XGBoost model incorporates a diverse range of hyperparameters,optimized by a genetic algorithm to improve its adaptability and generalization *** validation confirms the effectiveness of the proposed feature optimization scheme,demonstrating the superior estimation performance of the proposed method in comparison with four baseline techniques.

关键词： Lithium-ion battery State of health Electrochemical impedance spectroscopy Extreme gradient boosting

新一代羟乙基淀粉与人血白蛋白在活体肝移植中安全性的比较

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麻醉与镇痛 2011年第1期7卷 84-91页

作者： Ahmed Mukhtar Fawzia Aboulfetouh Gihan Obayah Maged Salah mohamed emam Yehia Khater Ramzia Akram Aly Hoballah mohamed Bahaa 沈文振(译) 岳云(校) Department of Anesthesia and Intensive Care Cairo University Giza Wadi-Alneel Liver Transplant Center Cairo Egypt Department of Surgery Ain Shams University Cairo Egypt 不详

背景血容量替代治疗是肝移植围手术期管理的重要部分。目前尚缺乏羟乙基淀粉（HES）应用于肝移植患者的相关安全性数据。我们评估了新一代羟乙基淀粉130／0．4应用于肝移植围手术期管理的安全性，并着重分析了其对肾功能的影响。方法行... 详细信息

背景血容量替代治疗是肝移植围手术期管理的重要部分。目前尚缺乏羟乙基淀粉（HES）应用于肝移植患者的相关安全性数据。我们评估了新一代羟乙基淀粉130／0．4应用于肝移植围手术期管理的安全性，并着重分析了其对肾功能的影响。方法行活体肝移植的40例患者被预先随机分成两组。ALB组患者（n=20）给予5％人血自蛋白，HES组（n=20）给予第三代羟乙基淀粉（6％HES130／0．4）。胶体总量被限制在50ml·kg^-1·d^-1，容量输注使肺小动脉楔压或中心静脉压维持在5—7mmHg。如需要额外的液体，则用平衡盐溶液替代。麻醉和手术操作过程均被标准化。分别测定麻醉诱导后、手术结束时、手术后前4天的动脉血肌酐和血清半胱氨酸蛋白酶抑制剂C（cystatin C）血浆水平。结果所有40例登记患者完成了研究。两组患者的人口统计学及手术中变量均具有可比性。手术后胶体液输入量分别是HES组6229±1140ml和ALB组4636±1153ml（P=0．003）。与ALB组（1100±900m1）相比，HES组（3047±2000ml）有更大的净累积液体平衡量（P=0．029）。两组血肌酐水平、肌酐清除率、cystafin C血浆水平差异无显著性。每组各有一例患者合并急性肾功能衰竭需行肾脏替代治疗。结论HES130／0．4做为人血白蛋白的替代品对肝移植术后肾功能的影响与后者相似。

关键词：羟乙基淀粉130 人血白蛋白活体肝移植安全性急性肾功能衰竭半胱氨酸蛋白酶抑制剂围手术期管理肝移植患者

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： mohamed Aghyad Al Kabbani Christoph Köhler Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

A Greener Future: Carbon Nanomaterials from Lignocellulose

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Journal of Renewable Materials 2025年第1期13卷 21-47页

作者： Hebat-Allah S.Tohamy mohamed El-Sakhawy Samir Kamel Cellulose and Paper Department National Research CentreDokkiGiza12622Egypt

Lignocellulosic materials(LCMs),abundant biomass residues,pose signiﬁcant environmental challenges when improperly disposed ***,such as sugarcane bagasse,rice straw,saw dust and agricultural residues,are abun-dant but often burned,contributing to air pollution and greenhouse gas *** review explores the potential of transforming these materials into high-value carbon nanomaterials(CNMs).We explore the potential of transforming these materials into high-value *** employing techniques like carbonization and activa-tion,LCMs can be converted into various CNMs,including carbon nanotubes(CNTs),graphene(G),graphene oxide(GO),carbon quantum dots(CQDs),nanodiamonds(NDs),fullerenes(F),carbon nanoﬁbers(CNFs),and *** different carbon allotropes further enhances their *** derived from cellulose,lignin,and hemicellulose exhibit promising applications in diverseﬁ*** instance,CNTs can be used in energy storage devices like batteries and supercapacitors due to their exceptional electrical conductivity and mechanical ***,CNTs can be incorporated into recycled paper as aﬁre retardant additive,enhancing itsﬂame resistance.G,renowned for its high surface area and excellent electrical conductivity,ﬁnds applications in electronics,sensors,catalysis,and water treatment,where it can be used to adsorb heavy metal ***,owing to their unique optical properties,are used in bioimaging,drug delivery,and optoelectronic *** harnessing the potential of LCMs,we can not only mitigate environmental concerns but also contri-bute to a sustainable *** research is essential to optimize synthesis methods,explore novel applica-tions,and unlock the full potential of these versatile materials.

关键词： Lignocellulosic materials carbon-based nanomaterials carbon allotropes

A Plastic Surgery Mission: Personal Experience in Improving Outcomes

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Modern Plastic Surgery 2025年第1期15卷 32-43页

作者： mohamed Elsayed mohamed mohamed Plastic Surgery Department Ahmed Maher Teaching Hospital Cairo Egypt

Background: Missions organized by international societies and humanitarian organizations play a significant role in saving many patients’ lives and improving their quality of life, despite the surrounding frustrating conditions. Methods: A team of plastic surgery volunteers was sent to Yemen by the KSHARC. Results: A successful mission was performed on 62 patients who underwent surgery, with more than 900 patients examined and receiving appropriate medications. Conclusion: Missions in disaster-affected areas are of great importance. The role of missions and humanitarian organizations should be empowered.

关键词： Missions Humanitarian Organizations Plastic Surgery Natural Disasters Wars