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Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

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Cancer Biology & Medicine 2015年第2期12卷 79-86页

作者： Niki Karachaliou Maria Gonzalez Cao Cristina teixid. Santiago Viteri Daniela Morales-Espinosa Mariacarmela Santarpia Rafael Rosell Instituto Oncológico Dr Rosell Quiron Dexeus University Hospital Pangaea Biotech Medical Oncology Unit Human Pathology Department University of Messina Catalan Institute of Oncology Hospital Germans Trias i Pujol Molecular Oncology Research (MORe) Foundation Germans Trias i Pujol Health Sciences Institute and Hospital

Survival rates for metastatic lung cancer, including non-small cell lung cancer(NSCLC) and small cell lung cancer(SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system—with its capacity for memory, exquisite specificity and central and universal role in human biology—immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

关键词：非小细胞肺癌免疫系统检查点癌症患者肿瘤发生免疫治疗人类生物学癌症治疗

Advances in immunotherapy for treatment of lung cancer

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Cancer Biology & Medicine 2015年第3期12卷 209-222页

作者： Jean G.Bustamante Alvarez María González-Cao Niki Karachaliou Mariacarmela Santarpia Santiago Viteri Cristina teixid. Rafael Rosell Albert Einstein Medical Center Translational Cancer Research Unit Instituto Oncológico Dr RosellQuirón Dexeus University Hospital Medical Oncology Unit Human Pathology Department University of Messina Pangaea Biotech S.L Cancer Biology & Precision Medicine Program Catalan Institute of Oncology Germans Trias i Pujol Health Sciences Institute and Hospital Campus Can Ruti Fundación Molecular Oncology Research

Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1(PD-1) and its ligand(PD-L1), on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab, another anti PD-1 antibody, has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer(NSCLC), supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.

关键词：非小细胞肺癌免疫治疗单克隆抗体程序性细胞死亡肿瘤细胞临床试验免疫反应反应活性

Depicting the battle between nectarine and Monilinia laxa:the fruit developmental stage dictates the effectiveness of the host defenses and the pathogen’s infection strategies

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Horticulture Research 2020年第1期7卷 619-633页

作者： Marta Balsells-Llauradó Christian J.Silva Josep Usall Núria Vall-llaura Sandra Serrano-Prieto Neus teixid. Saskia D.Mesquida-Pesci Antonieta de Cal Barbara Blanco-Ulate Rosario Torres IRTA XaRTA-PostharvestEdifici FruitcentreParc Científic i Tecnològic Agroalimentari de Lleida25003 LleidaCataloniaSpain Department of Plant Sciences University of CaliforniaDavisDavisCA 95616USA Department of Plant Protection INIACtra.de La Coruña Km.728040 MadridCommunity of MadridSpain

Infections by the fungus Monilinia laxa,the main cause of brown rot in Europe,result in considerable losses of stone ***,we present a comprehensive transcriptomic approach to unravel strategies deployed by nectarine fruit and *** during their *** used ***-inoculated immature and mature fruit,which was resistant and susceptible to brown rot,respectively,to perform a dual RNA-Seq *** immature fruit,host responses,pathogen biomass,and pathogen transcriptional activity peaked at 14–24 h post inoculation(hpi),at which point *** appeared to switch its transcriptional response to either quiescence or *** fruit experienced an exponential increase in host and pathogen activity beginning at 6 *** analyses in both host and pathogen highlighted differences in stage-dependent *** example,in immature fruit,*** unsuccessfully employed carbohydrate-active enzymes(CAZymes)for penetration,which the fruit was able to combat with tightly regulated hormone responses and an oxidative burst that challenged the pathogen’s survival at later time *** contrast,in mature fruit,*** was more dependent on proteolytic effectors than CAZymes,and was able to invest in filamentous growth early during the *** analyses of mature fruit infected with *** indicated that,while jasmonic acid activity was likely useful for defense,high ethylene activity may have promoted susceptibility through the induction of ripening ***,we identified *** genes that were highly induced in both quiescent and active infections and may serve as targets for control of brown rot.

关键词： fruit pathogen strategies

Erratum to Assays for predicting and monitoring responses to lung cancer immunotherapy

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Cancer Biology & Medicine 2015年第3期12卷 259-259页

作者： Cristina teixid. Niki Karachaliou Maria González-Cao Daniela Morales-Espinosa Rafael Rosell Pangaea Biotech Quirón Dexeus University Hospital Dr. Rosell Oncology Institute Quirón Dexeus University Hospital Cancer Biology and Precision Medicine Program Catalan Institute of OncologyHospital Germans Trias i Pujol

In the published article1,one error appeared on page *** has not yet received FDA approval for NSCLC *** October 2014 pembrolizumab received FDA breakthrough therapy designation for lung cancer treatment supported by ... 详细信息

关键词： lung Erratum to Assays for predicting and monitoring responses to lung cancer immunotherapy

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线条的秩序美

现代装饰 2019年第7期 90-95页

作者： Accardi Buccheri Cara\Davide Debonademeo Vivlana Degrandi Fran Silvestre Claesson Koivisto Rune Gabriel teixid. 李薇(编译) 不详

亚里士多德认为,美的主要形式是'秩序、匀称与明确',美就是'整一性'。'整一性'既不是单一,也不是杂多,而是像音乐一样,五律调和,八音和谐,在复杂丰富的多样性中又保持统一。秩序美是音乐、美术、设计等艺术创作的美的形式规律之一,在重... 详细信息

亚里士多德认为,美的主要形式是'秩序、匀称与明确',美就是'整一性'。'整一性'既不是单一,也不是杂多,而是像音乐一样,五律调和,八音和谐,在复杂丰富的多样性中又保持统一。秩序美是音乐、美术、设计等艺术创作的美的形式规律之一,在重复、渐变、规律的变化中,使设计或艺术展现出一种节奏或韵律。线条不论在设计中还是在艺术中都是最为简单的一种表现元素,运用线条的曲直、长短、疏密的变换可以赋予作品不同的张力与美感。

关键词：家具产品秩序美

IHC、FISH和RT-PCR检测对EML4-ALK重排的一致性

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临床与病理杂志 2015年第2期35卷 189-193页

作者： Cristina teixid. Niki Karachaliou Vicente Peg Ana Gimenez-Capitan Rafael Rosell 魏建国许春伟张博 Pangaea Biotech Quirón Dexeus University Institute Dr Rosell Oncology Institute Quirón Dexeus University Institute Catalan Institute of Oncology Hospital Germans Triasi Pujol 浙江省绍兴市人民医院病理科浙江绍兴312000 解放军307医院病理科北京100071

棘皮动物微管结合蛋白-间变性淋巴瘤激酶（echinoderm microtubule-associated prote i n-l ike4-anaplastic lymphoma kinase,EML4-ALK）在肺癌中已成为第二个最重要的驱动致癌基因,在4%-6%的肺腺癌中EML4-ALK已经成为第一个可以靶向治疗的融合基因位点。伴随着ALK分离探针荧光原位杂交（fluorescent in situ hybridization,FISH）试剂盒的上市,克唑替尼已经被批准治疗ALK阳性的进展期非小细胞肺癌（non-small cell lung cancer,NSCLC）。然而,一种靶向药物的成功主要取决于一种敏感且特异的筛选实验方法来检测分子药物作用的靶点。以作者的经验看,用RTPCR来检测EML4-ALK,比用FISH和免疫组化（immunohistochemistry,IHC）方法更敏感,结果更可靠。尽管通过FISH检测ALK已经经过大量的临床实验验证,然而该方法在技术层面仍存在许多具有挑战性的问题,而通过IHC和RT-PCR方法检测ALK仍需要临床进一步的探索。

关键词：间变性淋巴瘤激酶(ALK) 荧光原位杂交(FISH) 免疫组化(IHC) 非小细胞肺癌(NSCLC) 逆转录聚合酶链反应(RT-PCR)

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ALK和ROS1:肺癌治疗的联合靶点

临床与病理杂志 2014年第1期34卷 1-14页

作者： Raimon Puig de la Bellacasa Niki Karachaliou Roger Estrada-Tejedor Jordi teixid. Carlota Costa José I.Borrell 吴冠楠(译) 宋勇(审校) Grup d’Enginyeria Molecular Institut Químic de SarriàUniversitat Ramon Llull Breakthrough Cancer Research Unit Pangaea Biotech S.L 南京大学医学院临床学院南京军区南京总医院呼吸内科南京210002

间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)基因重排可见于包括非小细胞肺癌(non small cell lung cancer,NSCLC)在内的多种恶性肿瘤中。ALK融合基因使激酶具有异常活性,而野生型ALK激酶域突变也可使它被激活。ALK基因重排使得N... 详细信息

间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)基因重排可见于包括非小细胞肺癌(non small cell lung cancer,NSCLC)在内的多种恶性肿瘤中。ALK融合基因使激酶具有异常活性,而野生型ALK激酶域突变也可使它被激活。ALK基因重排使得NSCLC中出现了新的分子亚型,该亚型对ALK抑制剂高度耐药。克唑替尼(crizotinib)是一个口服小分子ATP模拟化合物,它最初作为MET抑制剂被开发,随后被发现具有抗ALK活性的脱靶效应(off target),并被美国FDA批准用于治疗ALK阳性的NSCLC患者。近来在NSCLC患者中还发现了ROS1受体酪氨酸激酶染色体重排,而克唑替尼正处于治疗该分子亚型NSCLC患者的临床试验中。任何计算机辅助药物设计都是依赖其分子结构和配体的药物设计方法,每种方法的详细信息中均应重点强调利用这二者,以开发多靶点小分子激酶抑制剂。此类多靶点小分子激酶抑制剂均可对ROS1和ALK重排的NSCLC有抑制增殖作用。因此,本综述重点强调了关于靶向这些激酶的重要性,以及在优化出效能更佳、选择性更强的ROS1和ALK激酶抑制剂中所取得的进步。

关键词：间变性淋巴瘤激酶药物设计激酶抑制剂非小细胞肺癌 ROS1

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T1期乳腺肿瘤术前腋窝超声检查的价值

国际医学放射学杂志 2016年第3期 334-334页

作者： J.del Riego M.J.Diaz-Ruiz M.teixid. J.Ribé M.Vilagran L.Canales 唐皓 Women’s Imaging Department of RadiologyUDIAT Centre DiagnòsticInstitut Universitari Parc Taulí-UAB

摘要目的 (1)探讨在p T1期肿瘤病人中腋窝超声检查(AUS)的诊断价值以及联合细针穿刺(FNA)能否提高诊断效能;(2)确定在满足美国外科医师协会(ACOSOG)Z0011标准的病人(淋巴结转移数目不超过2个)中腋窝超声检查的阴性预测值。材料与方法在... 详细信息

摘要目的 (1)探讨在p T1期肿瘤病人中腋窝超声检查(AUS)的诊断价值以及联合细针穿刺(FNA)能否提高诊断效能;(2)确定在满足美国外科医师协会(ACOSOG)Z0011标准的病人(淋巴结转移数目不超过2个)中腋窝超声检查的阴性预测值。材料与方法在355例p T1期乳腺肿瘤病人中,采

关键词：腋窝细针穿刺乳腺肿瘤 T1 超声检查