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new avenues for the treatment of immunotherapy-resistant pancreatic cancer

World Journal of Gastrointestinal Oncology 2024年第4期16卷 1134-1153页

作者： luis Guilherme de Oliveira Silva Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Mariana dos Santos calmon Gabriel Lima correa Santos Gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Pancreatic cancer(pc)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases ***,due to its complexity,it ranks 7th in the list of the most lethal cancers *** pathogenesis of pc involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and *** in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,*** this context,some therapies are used for pc,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of pc due to various resistance mechanisms that contribute to a drop in immunotherapy *** is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive *** to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of cD8+T cells and limited expression of activation markers such as *** this way,finding new strategies that make it possible to manipulate resistance mechanisms is ***,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRnAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of pc ***,this study aims to elucidate the main mechanisms of resistance to immunotherapy in pc and new ways of manipulating thi

关键词： Pancreatic cancer Immunotherapy Resistance Tumor microenvironment manipulation combined immunotherapy

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Multi-omic study to unmask genes involved in prostate cancer development in amulti-case family

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cancer communications 2024年第3期44卷 443-447页

作者： Lucia chica-Redecillas Sergio cuenca-Lopez Eduardo Andres-Leon Laura carmen Terron-camero Blanca cano-Gutierrez Jose Manuel cozar Jose Antonio Lorente Fernando Vazquez-Alonso luis Javier Martinez-Gonzalez Maria Jesus Alvarez-cubero GEnYO Centre for Genomics and Oncological ResearchPfizerUniversity of GranadaAndalusian Regional GovernmentPTS GranadaGranadaGranadaSpain Department of Biochemistry Molecular Biology III and ImmunologyFaculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Bioinformatics Unit Institute of Parasitology and Biomedicine“López-Neyra”Spanish National Research CouncilGranadaGranadaSpain nursery Service.University Hospital clínico San cecilio GranadaGranadaSpain Urology Department University Hospital Virgen de las NievesGranadaGranadaSpain Legal Medicine and Toxicology Department Faculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Ibs Biosanitary Research InstituteGranadaGranadaSpain

Dear Editor,Hereditary prostate cancer(pc)comprises 5%-10%of all pc *** increased risk of pc in menwith a family his-tory of the disease is well known and is commonly caused by germline mutations,leading to clinical guidelines men-tioning various genes for identifying high-risk ***,the complex inheritance patterns involvingmul-tiple single nucleotide polymorphisms(SnPs)make it a genetically heterogeneous disease,with genetic testing still in its early stages.

关键词： cancer clinical cases

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Anatomical characterization of central, apical and minimal corneal thickness

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International Journal of Ophthalmology(English edition) 2014年第4期7卷 668-672页

作者： Federico Saenz-Frances Martha cecilia Bermúdez-Vallecilla Lara Borrego-Sanz luis Jaez J osé Marìa Martinez-de-la-casa Laura Morales-Fernandez Enrique Santos-Bueso Julián Garcia-Sanchez Julián Garcia-Feijoo Department of Ophthalmology Hospital Clínico San CarlosUniversidad Complutense de Madrid Instituto de Tecnologìa del conocimiento Universidad Complutense de Madrid

·AIM: To anatomically locate the points of minimum corneal thickness and central corneal thickness(pupil center) in relation to the corneal apex.·METHODS: Observational, cross-sectional study, 299 healthy volunteers. Thickness at the corneal apex(AT),minimum corneal thickness(MT) and corneal thickness at the pupil center(PT) were determined using the pentacam. Distances from the corneal apex to MT(MD)and PT(PD) were calculated and their quadrant position(taking the corneal apex as the reference) determined:point of minimum thickness(Mc) and point of central thickness(pc) depending on the quadrant position. Two multivariate linear regression models were constructed to examine the influence of age, gender, power of the flattest and steepest corneal axes, position of the flattest axis, corneal volume(determined using the Pentacam)and PT on MD and PD. The effects of these variables on Mc and pc were also determined in two multinomial regression models.·RESULTS: MT was located at a mean distance of 0.909 mm from the apex(79.4% in the inferior-temporal quadrant). PT was located at a mean distance of 0.156 mm from the apex. The linear regression model for MD indicated it was significantly influenced by corneal volume(B =-0.024; 95% cI:-0.043 to-0.004). no significant relations were identified in the linear regression model for PD or the multinomial logisticregressions for Mc and pc.·cOncLUSIOn: MT was typically located at the inferiortemporal quadrant of the cornea and its distance to the corneal apex tended to decrease with the increment of corneal volume.

关键词： cornealthickness anatomy glaucoma

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The Role of the Southern Hemisphere Polar cell on Antarctic Sea Ice Variability

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International Journal of Geosciences 2016年第2期7卷 120-134页

作者： Praveen Rao Teleti Alvarinho J. luis Earth System Science Organization National Centre for Antarctic and Ocean Research Ministry of EarthSciences Govt. of India Headland Sada Goa India

The study explores modes of variability in the Southern Polar cell and their relationship with known global climate modes and Antarctic sea ice. It is found that Polar cell is barotropic in nature and 500 hPa geo-potential height (Z500) field can satisfactorily represent variability in the Polar cell. First, three leading Empirical Orthogonal Function (EOF) modes of Z500 account for nearly 80% of observed variability in the Polar cell. Dominant mode (pc1500) comprises of high pressure divergence zone over Antarctica. Second leading mode (pc2500) is low pressure zone covering Amundsen-Bellingshausen Sea (ABS) similar to ABS low feature. A new climate mode called Polar coastal Index (pcI) is defined, which describes more than 15% and close to 30% variability of circumpolar trough and ABS low, respectively. Out of four modes defined in this study, only pcI and pc2500 show linear trends and clear seasonality. Interestingly, both modes are affected by modulation of ABS low due to tropical EnSO forcing. SAM signature is present in Polar cell as pc1500 shares large variance with it. The largest impact on sea ice comes from pc2500 followed by pc1500 in the Antarctic Dipole regions. However, this study suggests contemporary sea ice trends cannot be sustained, and can reverse given that trends in pcI and pc2500 favour a reversal. These results indicate that EnSO-driven Polar cell variability plays a crucial role influencing Antarctic sea ice as it interacts with other climate modes and leads the combined impact at the interannual time scale.

关键词： Antarctica Sea Ice Polar cell pcI EnSO Teleconnection

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帕博利珠单抗联合以铂类为基础的化疗治疗非小细胞肺癌合并稳定性脑转移患者的结局:KEYnOTE-021、-189和-407研究的汇总分析

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中国肺癌杂志 2022年第1期25卷 I0007-I0018页

作者：周清(翻译校对) Steven F Powell Delvys Rodríguez-Abreu corey J Langer Ali Tafreshi luis Paz-Ares Hans-Georg Kopp Jeronimo Rodríguez-cid Dariusz M Kowalski Ying cheng Takayasu Kurata Mark M Awad Jinaxin Lin Bin Zhao M catherine Pietanza Bilal Piperdi Marina c Garassino 广东省人民医院肺三科广东省医学科学院广东省肺癌研究所广州510080 Sanford Health Sioux FallsSouth Dakota complejo Hospitalario Universitario Insular-Materno Infantil Universidad de Las Palmas de Gran CanariaGran CanariaSpainospital Universitario Insular de Gran CanariaLas Palmas de Gran CanariaLas Palmas de Gran CanariaSpain Abramson cancer center University of PennsylvanialadelphiaPennsylvania Wollongong Private Hospital University of WollongongWollongongAustralia Hospital Universitario 12 de Octubre CNIOUniversidad Complutense and CiberoncMadridSpain Robert Bosch centrum für Tumorerkrankungen Robert Bosch Cancer CenterKlinik SchillerhoheGerlingenGermany Oncology center Médica Sur Hospital-Instituto Nacional de Enfermedades RespiratoriasMexico CityMexico Maria Sklodowska-curie national Research Institute of Oncology WarsawPoland Jilin cancer Hospital ChangchunJilinPeople's Republic of China Department of Thoracic Oncology Kansai Medical University HospitalHirakataOsakaJapan Massachusetts General Hospital cancer center and Harvard Medical School BostonMassachusetts Merck Sharp&Dohme corp. a subsidiary of Merck&Co.Inc.KenilworthNew Jersey Fondazione Istituto di Ricovero e cura a carattere Scientifico Istituto nazionale dei Tumori MilanItaly

背景与目的此项探索性分析回顾评价了晚期非小细胞肺癌(non-small cell lung cancer,nScLc)患者的结局,旨在确定基线时合并脑转移是否会影响一线应用帕博利珠单抗联合化疗(pembrolizumab plus chemotherapy,pc)比对单用化疗的疗效。患... 详细信息

背景与目的此项探索性分析回顾评价了晚期非小细胞肺癌(non-small cell lung cancer,nScLc)患者的结局,旨在确定基线时合并脑转移是否会影响一线应用帕博利珠单抗联合化疗(pembrolizumab plus chemotherapy,pc)比对单用化疗的疗效。患者和方法对KEYnOTE-021队列G(非鳞癌)、KEYnOTE-189(非鳞癌)和KEYnOTE-407(鳞癌)三项研究晚期nScLc患者的数据进行汇总分析。患者接受含铂两药化疗和/或35个周期帕博利珠单抗治疗(每3周200 mg)。所有研究均纳入了经治或初治的稳定性脑转移患者(KEYnOTE-189与KEYnOTE-407研究纳入初治脑转移患者)。经治的脑转移患者已处于病情稳定的状态≥2周(KEYnOTE-021队列G患者≥4周),无新发或脑转移病灶扩大的证据且入组前至少3天以上未使用激素。初治的无症状脑转移患者需定期接受脑部影像学检查。结果共纳入1298例患者,其中171例有基线脑转移,1127例无脑转移。两组的中位随访时间(范围)在数据截止时分别为10.9(0.1-35.1)个月和11.0(0.1-34.9)个月。合并脑转移和无脑转移患者的总生存期[0.48(95%cI:0.32-0.70)和0.63(95%cI:0.53-0.75)]和无进展生存期[0.44(95%cI:0.31-0.62)和0.55(95%cI:0.48-0.63)]的风险比(pc/化疗)相似。合并脑转移的患者中,pc组和单用化疗组患者的中位总生存期分别为18.8个月和7.6个月,中位无进展生存期分别为6.9个月和4.1个月。无论是否合并脑转移,pc组患者的客观缓解率都高于单用化疗组,且缓解持续时间有显著延长。合并脑转移的患者中,pc组与单用化疗组的治疗相关不良事件发生率分别为88.2%和82.8%;而无脑转移的患者中,两组治疗相关不良事件的发生率分别为94.5%和90.6%。结论无论是否合并脑转移,与单用化疗相比,帕博利珠单抗联合以铂类为基础的组织学特异性化疗可改善所有PD-L1亚组的临床结局,其中包括PD-L1肿瘤比例评分nScLc患者中安全性良好。该方案是晚期nScLc初治患者的标准方案,并可用于合并稳定性脑转移的患者。

关键词：帕博利珠单抗脑转移化疗非小细胞肺癌 PD-L1

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A comprehensive Evaluation of PAn-Sharpening Algorithms coupled with Resampling Methods for Image Synthesis of Very High Resolution Remotely Sensed Satellite Data

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Advances in Remote Sensing 2013年第4期2卷 332-344页

作者： Shridhar D. Jawak Alvarinho J. luis Polar Remote Sensing Department Earth System Sciences Organization (ESSO) National Centre for Antarctic and Ocean Research (NCAOR) Ministry of Earth Sciences Government of India Headland Sada Gao India

The merging of a panchromatic (PAn) image with a multispectral satellite image (MSI) to increase the spatial resolution of the MSI, while simultaneously preserving its spectral information is classically referred as PAn-sharpening. We employed a recent dataset derived from very high resolution of WorldView-2 satellite (PAn and MSI) for two test sites (one over an urban area and the other over Antarctica), to comprehensively evaluate the performance of six existing PAn-sharpening algorithms. The algorithms under consideration were the Gram-Schmidt (GS), Ehlers fusion (EF), modified hue-intensity-saturation (Mod-HIS), high pass filtering (HPF), the Brovey transform (BT), and wavelet-based principal component analysis (W-pc). Quality assessment of the sharpened images was carried out by using 20 quality indices. We also analyzed the performance of nearest neighbour (nn), bilinear interpolation (BI), and cubic convolution (cc) resampling methods to test their practicability in the PAn-sharpening process. Our results indicate that the comprehensive performance of PAn-sharpening methods decreased in the following order: GS > W-pc > EF > HPF > Mod-HIS > BT, while resampling methods followed the order: nn > BI > cc.

关键词： PAn-Sharpening WorldView-2 Resampling Methods

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Optical Microscopy as a Tool to correlate Morphology and Thermal Properties of Extruded PET/pc Reactive Blends

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Materials Sciences and Applications 2011年第8期2卷 1033-1040页

作者： luis claudio Mendes Patricia Soares da costa Pereira Instituto de Macromoléculas Professora Eloisa Mano-IMA Universidade Federal do Rio de Janeiro-UFRJ Centro de Tecnologia Bloco J P.O.Box 68525 Avenida Horácio Macedo 2030 -21941-598 Rio de Janeiro RJ Brasil

catalysed and uncatalysed reactive extruded poly(ethylene terephthalate)/poly(bisphenol-A carbonate) (PET/pc) blends phase structure at compositional range containing 0-100 wt% of both parent polymers were evaluated. Phase separation was supported by TG/DTG, DMA and DSc. The changes on Tg and Tm of the parent polymers were associated to the esterification and transesterification reactions inside the phases and into the interfacial region. According to optical observations, not yet published in this matter, the blend morphology was dictated, either composition or melt flow rate and in the whole composition range, a matrix-droplet morphology was noticed. PET was only able to be crystallized in blends in which it was the matrix. Mostly, the PET/pc blends revealed to be partially miscible systems in which the level of the transesterification/esterification reactions was driven by the kind of matrix. The latter showed great influence on the thermal properties.

关键词： PET/pc Phase Structure Morphology OM DMA DSc TG/DTG

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Detection of circulating tumor cells in blood of pancreatic ductal adenocarcinoma patients

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cancer Drug Resistance 2020年第1期3卷 83-97页

作者： Andrea Mayado Alberto Orfao Anouk Mentink Maria Laura Gutierrez luis Muñoz-Bellvis Leon W.M.M.Terstappen cancer Research center(IBMcc-cSIc/USAL-IBSAL) Cytometry Service(NUCLEUS)and Department of MedicineUniversidad de SalamancaSalamanca 37007Spain centro de Investigación Biomédica en Red de cáncer(cIBER-Onc)cB16/12/00400 Instituto de Salud Carlos IIIMadrid 28029Spain Department of Medical cell BioPhysics University of TwenteEnschede 7522The Netherlands Division of General and Gastrointestinal Surgery University Hospital of Salamanca(CAUSA)and Department of SurgeryUniversidad de Salamanca and IBSALSalamanca 37007Spain

Aim:Previous studies suggest that circulating tumor cells(cTc)are present at very low frequencies in blood of pancreatic cancer(pc)***,no technique has proven efficient for their detection,in part due to the lack of accurate tumor ***,we evaluated the potential utility of two marker candidates-Mucin 16(MUc16)and Tetraspanin 1(TSPAn1)-identified through a detailed review of the ***:To evaluate the pattern of expression of both markers in pancreatic tumor cells *** blood,we used cell lines derived from pancreatic cancer patients and blood from healthy ***:Antibodies against both MUc16 and TSPAn1 showed expression in three pancreatic cancer(pc)cell lines while they were absent in blood *** evaluate the efficiency of isolating tumor cells from blood,pc cell lines were spiked at different frequencies in blood,sequentially stained with biotin-conjugated TSPAn1 and MUc16 antibodies and a streptavidin ferrofluids,followed by immunomagnetic *** recovery of spiked TSPAn1+tumor cells was high with limited contamination by *** contrast,no pc cells were isolated when the biotin MUc16 reagent was used because the biotin-conjugated clone did not recognize pc ***:The combination of MUc16,TSPAn1,and epithelial cell adhesion molecule(EpcAM)antibodies will likely increase the efficiency of capturing circulating tumor cell in blood of pancreatic ductal *** further develop a protocol for isolation of circulating tumor cell in blood of pc patients,high amounts of antibodies(5-10 mg)against EpcAM,MUc16,and TSPAn1 will be needed.

关键词： Pancreatic ductal adenocarcinoma circulating biomarkers circulating tumor cells

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Synthesis and Structure of novel Hexa-histidine cyclopeptide with Potential in Biomimetic and Medicinal chemistry

Synthesis and Structure of Novel Hexa-histidine Cyclopeptide...

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第四届全国化学生物学学术会议暨国际化学与生物/医学交叉研讨会

作者：周成合 SantiagoV．luis School of Pharmaceutical Sciences chongqing Medical University Chongqing 400016 School of Chemistry and Chemical EngineeringSouthwest UniversityChongqing400715 Department of Inorganicand Organic chemistry Universitat JaumeI Castellon12080Spain

A novel hexa-histidine cyclopeptide(1)with potential as biomimetic model,anti—HIV agent and Histamine H3 receptor modulator was prepared through 12-step reactions from *** compounds were characterized by 1H,13c,1H-15...

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clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer

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cancer Biology & Medicine 2020年第2期17卷 444-457页

作者： Juan Moreno-Rubio Santiago Ponce Rosa Alvarez Maria Eugenia Olmedo Sandra Falagan Xabier Mielgo Fatima navarro Patricia cruz luis cabezon-Gutierrez carlos Aguado Gonzalo colmenarejo Marta Munoz-Fernandez de Leglaria Ana Belen Enguita Maria cebollero Amparo Benito Isabel Alemany carolina del castillo Ricardo Ramos Ana Ramirez de Molina Enrique casado Maria Sereno Ana Ramirez de Molina1 Enrique Casado5Maria Sereno5 XIMDEA Food InstituteCEI UAM+CSICMadrid 28702Spain 12 de Octubre University Hospital Madrid 28041Spain Gregorio Maranon University Hospital Madrid 28009Spain Ramon y cajal University Hospital Madrid 28034Spain Infanta Sofia University Hospital San Sebastian De Los ReyesMadrid 28702Spain Fundacion Alcorcon University Hospital AlcorconMadrid 28922Spain Prlncipe de Asturias University Hospital Alcala De HenaresMadrid 28805Spain La Paz University Hospital Madrid 28046Spain University Hospital of Torrejon Torrejon De ArdozMadrid 28850Spain clinico San carlos University Hospital Madrid 28040Spain Parque cientifico de Madrid Foundation Madrid 28049Spain

Objective:Long-term survivors(LS)of non-small cell lung cancer(nScLc)without driver alterations,displaying an overall survival(OS)of more than 3 years,comprise around 10%of cases in several series treated with *** are classical prognosis factors for these cases[stage,Eastern cooperative Oncology Group(EcOG),etc.],but more data are required in the *** this multi-center study,we focused on LS of advanced nScLc with OS above 36 months to perform a clinical-pathological and molecular ***:In the first step,we conducted a clinical-pathological characterization of the ***,we carried out a genetic analysis by comparing LS to a sample of short-term survivors(SS)(with an OS less than 9 months).We initially used whole-genome RnA-seq to identify differentiating profiles of LS and SS,and later confirmed these with reverse transcription-polymerase chain reaction(RT-pcR)for the rest of the ***:A total of 94 patients were included,who were mainly men,former smokers,having adenocarcinoma(Ac)-type nScLc with an EcOG of *** obtained an initial differential transcriptome expression,displaying 5 over-and 33 under-expressed genes involved in different pathways:namely,the secretin receptor,surfactant protein,trefoil factor 1(T FF1),serpin,ca-channels,and Tolllike receptor(TLRs)***,RT-pcR analysis of 40(20 LS/20 SS)samples confirmed that four genes(surfactant proteins and SFTP)were significantly down-regulated in SS compared to LS by using an analysis of covariance(AncOVA)model:SFTPA1(P=0.023),SFTPA2(P=0.027),SFTPB{P=0.02),and SFT pc(P=0.047).conclusions:We present a sequential genetic analysis of a sample of nScLcLS with no driver alterations,obtaining a differential RnA-seq/RT-pcR profile showing an abnormal expression of SF genes.

关键词： Long-term survivors non-small cell lung cancer surfactant proteins

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