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| 1 | Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy显示文摘It remains unclear why the clinically used anti-CTLA-4 antibodies, popularly called checkpoint inhibitors, have severe immunotherapy-related adverse effects (irAEs) and yet suboptimal cancer immunotherapeutic effects (CITE). Here we report that while irAE-prone Ipilimumab and TremeIgG1 rapidly direct cell surface CTLA-4 for lysosomal degradation, the non-irAE-prone antibodies we generated, HL12 or HL32, dissociate from CTLA-4 after endocytosis and allow CTLA-4 recycling to cell surface by the LRBA-dependent mechanism. Disrupting CTLA-4 recycling results in robust CTLA-4 downregulation by all anti-CTLA-4 antibodies and confers toxicity to a non-irAE-prone anti-CTLA-4 mAb. Conversely, increasing the pH sensitivity of TremeIgG1 by introducing designed tyrosine-to-histidine mutations prevents antibody-triggered lysosomal CTLA-4 downregulation and dramatically attenuates irAE. Surprisingly, by avoiding CTLA-4 downregulation and due to their increased bioavailability, pH-sensitive anti-CTLA-4 antibodies are more effective in intratumor regulatory T-cell depletion and rejection of large established tumors. Our data establish a new paradigm for cancer research that allows for abrogating irAE while increasing CITE of anti-CTLA-4 antibodies. | Yan Zhang Xuexiang Du Mingyue Liu Fei Tang Peng Zhang Chunxia Ai James K. Fields Eric J. Sundberg Olga S. Latinovic Martin Devenport Pan Zheng Yang Liu | 2019 | Cell Research2019，29，8： | 6 |
| 2 | Health care in light of different theories of health——A proposed framework for integrating a social humanistic perspective into health care显示文摘The objective of this paper is to provide an overview of the biomedical,the biopsychosocial, and the social humanistic theories of health and to propose a framework for integrating the latter into health care. In summary, the definitions of health, illness and disease are essential to the practice of health care and play fundamental roles in how patients’ experiences of being ill are valued and assessed within health care systems. Principally, the biomedical perspective proceeds from pathoanatomical deficiencies defining disease and malfunction;the addition of psychosocial components forms a biopsychosocial perspective.In addition, the social humanistic perspective extends from a person’s will, their ability to act, and the possibility to fulfill wanted actions. Thus, health care that does not address the social humanistic perspective may lack the power to describe how these entities are related to the patient on a personal level;thus,the will of the patient is not always fully addressed. Importantly, by targeting the will of the patient and the patient’s ability to act, the proposed framework of integrating a social humanistic perspective into health care may further emphasize and strengthen the interrelatedness of medical perspectives. A framework for integrating a social humanistic perspective into health care is proposed and its potential impact on health care is discussed. | Lena Gronblom Lundstrom Ulrika Aasa Yan Zhang Tobias Sundberg | 2019 | Journal of Integrative Medicine2019，17，5： | 6 |
| 3 | Transcriptome Analysis of High-Temperature Stress in Developing Barley Caryopses: Early Stress Responses and Effects on Storage Compound Biosynthesis显示文摘高温度的应力象任何不能生活的压力一样,损害植物的生理学和发展,包括种子设定并且成熟的阶段。我们使用了调查开发大麦(Hordeum vulgare ) 的反应的 GeneChip microarray 播种的 Affymetrix 22K Barley1,称为的 caryopses 在 0.5 以后, 3,和 6 ? 热压力暴露的 h;958 导致了, 1122 镇压了空间的展出的基因和提供详细卓见进 caryopse 的早热的时间的表示模式强调回答。与存储混合物生合成和细胞生长有关的基因的下面规定为 caryopsi 的发展的一个快速的缺陷提供证据。糖和氨基酸的增加的层次为兼容溶质的生产和为存储混合物生合成的底层的导致反馈的累积是指示的。当热的主要地点强调回答,元数据分析识别了胚胎和内乳,显示颖果的中央发展函数上的短期的热应力的强壮的影响。有在 Arabidopsis 射击的热压力回答和在大麦 caryopses 的干旱压力回答的比较识别了保存并且大概热特定、颖果特定的压力应答的基因。总结,我们的数据提供一个重要基础让基因功能的进一步的调查以便为谷物庄稼作为一个模型在大麦帮助改进的热忍耐和产量的减少的损失。 | Elke Mangelsen Joachim Kilian Klaus Harter Christer Jansson Dierk Wanke Eva Sundberg | 2011 | Molecular Plant2011，4，1： | 6 |
| 4 | Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms显示文摘 | Ida Rasmusson Olle Ringdén Berit Sundberg Katarina Le Blanc | 2005 | Experimental Cell Research2005，，1： | 2 |
| 5 | Pharmacogenomics and individualized drug therapy显示文摘 | Eichelbaum M Ingelman - Sundberg M Evans WE | 2006 | Annu Rev Med2006，57，： | 1 |
| 6 | Multistrea m hybrid in band on channel FM systems for digital audio broadcasting显示文摘 | Deepen Sinha David Mansour | 1999 | IE EE Transactions on Broadcasting1999，45，4： | 1 |
| 7 | The role of the hairless (hr) gone in the regulation of hair follicle catagen transformation显示文摘 | Panteleyev AA Botchkareva NV Sundberg JP | 1999 | Am J Pathol1999，155，1： | 1 |
| 8 | The 104 125 amino acid sequence of the beta-domain of yon HippeI--Lindau gene product is sufficient to inhibit renal tumor growth and fnvasion显示文摘 | Datta K Sundberg C Karumanchis A | 2001 | Oancer Res2001，61，5： | 1 |
| 9 | Multistream hybrid in band on channel FM systems for digital audio broadcasting 显示文摘 | Sundberg Carl-Erik W Sinha Deepen Mansour David | 1999 | IEEE Transactions on Broadcasting1999，45，4： | 1 |
| 10 | Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells显示文摘 | Le Blanc K Rasmusson I Sundberg B | | 0，，9419： | 1 |
| 11 | Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development显示文摘 | Hansen L A Alexander N Hogan M E Sundberg J P Dlugosz A Threadgill D W Magnuson T Yuspa S H | | 0，，06： | 1 |
| 12 | Interactions between dissolved and colloidal substances and a cationic fixing agent in me- chanical pulp suspensions 显示文摘 | Sundberg A Ekman R Holmbom B | 1993 | Nordic Pulp and Paper Research Journal1993，8，1： | 1 |
| 13 | Pharmacogenetics of cytochrome P450 and its application in drug therapy: the past, present, and future 显示文摘 | Ingelman - Sundberg M | 2004 | Trends Pharmacol Sci2004，25，： | 1 |
| 14 | Fish intake of Swedish male adolescents is a predictor of cognitive performance 显示文摘 | Aberg MA Aberg N Brisman J Sundberg R Winkvist A Toren K | 2009 | Acta Paediatr2009，98，3： | 1 |
| 15 | Influence of different grinding methods on floatability 显示文摘 | Eric Forssberg Stellan Sundberg Zhai Hongxin | 1988 | International Journal of Mineral Processing1988，22，1： | 1 |
| 16 | Tissue repair using allogeneic mesenchymal stem cells for hemorrhagic cystitis,pneumomediastinum and perforated colon显示文摘 | Ringdén O Uzunel M Sundberg B | 2007 | Leukemia2007，21，11： | 1 |
| 17 | Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompati- bility compelx显示文摘 | Le Blanc K Tammik C Sundberg B | 2003 | Scand J Immunol2003，57，： | 1 |
| 18 | Microencapsulation of emulsified oil droplets by in-situ vinyl polymerization显示文摘 | Berg J Sundberg D C Kronberg B J | | 0，，： | 1 |
| 19 | Molecular interactions in interleukin and toll-like receptor signaling pathways 显示文摘 | Snyder GA Sundberg EJ | 2014 | Curr Pharm Des2014，20，8： | 1 |
| 20 | The immunomodulatory benzodiazepine Bz-423 inhibits B-cell proliferation by targeting c-myc protein for rapid and specific degradation 显示文摘 | SUNDBERG T B NEY G M SUBRAMANIAN C | 2006 | Cancer Res2006，66，3： | 1 |
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