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Molecular profiling and patient selection for the multimodal approaches for patients with resectable colorectal liver metastases

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Hepatobiliary Surgery and Nutrition 2024年第2期13卷 273-292页

作者： Raphael L.C.Araujo leonardo g.fonseca Raphael Oliveira Silva Marcelo Moura Linhares Pedro L.S.Uson Junior Department of Surgery Universidade Federal de São PauloSão PauloSPBrazil Hospital e Maternidade Brasil-Rede D’Or São Luiz Santo AndréSPBrazil Department of Oncology Hospital Israelita Albert EinsteinSão PauloSPBrazil Department of Oncology Instituto do Cancer do Estado de São PauloUniversity of Sao PauloSão PauloSPBrazil Department of Oncology Hospital Ministro Costa CavalcantiFoz do IguaçuPRBrazil Center for Personalized Medicine Hospital Israelita Albert EinsteinSão PauloSPBrazil

Colorectal cancer represents the third most common cancer and about 20%are diagnosed with synchronous metastatic *** a historical point of view,surgery remains the mainstream treatment for resectable colorectal liver metastases(CRLM).Furthermore,disease outcomes are improving due significant advances in systemic treatments and diagnostic ***,the optimal timing for neoadjuvant chemotherapy or upfront surgery for CRLM has not yet been established and remains an open ***,patient selection combining image workouts,time of recurrence,positive lymph nodes,and molecular biomarkers can improve the decision-making ***,molecular profiling is rising as a promising field to be incorporated in the multimodal approach and guide patient selection and sequencing of *** biomakers,genetic profiling,and circulating tumor DNA have been used to offer as much personalized treatment as possible,based on the precision oncology concept of tailored care rather than a guideline-based *** review article discusses the role of molecular pathology and biomarkers as prognostic and predictor factors in the diagnosis and treatment of resectable CRLM.

关键词： Colorectal liver metastases(CRLM) surgery chemotherapy molecular pathology circulating tumor DNA tumor markers

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Updates in immunotherapy for hepatocellular carcinoma

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Hepatoma Research 2019年第10期5卷 19-31页

作者： leonardo g.da fonseca Flair JoséCarrilho Medical Oncology São Paulo Clínicas Liver Cancer GroupHospital das Clínicas ComplexInstituto do Cancer do Estado de São PauloUniversity of São Paulo School of MedicineSão PauloSP 05403-000Brazil Department of gastroenterology São Paulo Clínicas Liver Cancer GroupHospital das Clínicas ComplexInstituto do Cancer do Estado de São PauloUniversity of São Paulo School of MedicineSão PauloSP 05403-000Brazil

Hepatocellular carcinoma(HCC)carries an unfavorable prognosis and novel therapeutic strategies are *** now,only few systemic agents have improved survival in patients with advanced stage *** changed the landscape in several tumor types by producing unprecedented clinical outcomes with a favorable safety *** presents a particular immune-suppressive microenvironment and HCC develops in a background of chronic inflammation in the vast majority of *** this regard,immunotherapy may be a suitable *** research focused on therapies involving immune cells and anti-tumor immune response for HCC has shown encouraging preliminary *** checkpoint inhibitors,such the anti-PD-1/PD-L1 monoclonal antibodies,have provided durable responses in patients with advanced stage disease,although the pioneers phaseⅢtrials did not confirm survival superiority over the available *** vaccines,adoptive cellular therapies and combinations of local modalities with immunotherapy are promising approaches under active research.

关键词： Hepatocellular carcinoma immunotherapy immunosuppression prognosis immunology antibody vaccine

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Trial eligibility in advanced hepatocellular carcinoma: Does it support clinical practice in underrepresented subgroups?

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World Journal of gastroenterology 2021年第24期27卷 3429-3439页

作者： Federico Piñero leonardo gomes da fonseca Hepatology and Liver Unit Hospital Universitario AustralSchool of MedicineAustral UniversityBuenos Aires B1629HJArgentina Clinical Oncology Insituto do Cancer do Estado de São PauloUniversity of São PauloSão Paulo 05403-000Brazil

Although hepatocellular carcinoma is considered a highly lethal malignancy,recent therapeutic advances have been achieved during the last 10 *** scenario resulted in an unprecedented improvement in survival for patients with advanced hepatocellular carcinoma,almost reaching 20-26 mo of overall survival after first-second line sequential *** advent of the combination of atezolizumab with bevacizumab showed,for the first time,superiority over sorafenib with improvement in overall ***,first and second-line trials were correctly based on the premise that a strict selection of patients enhances the power to capture the positive effect of treatment by excluding competing risks for mortality such as liver failure,decompensated cirrhosis or other underlying medical *** a result,the inclusion criteria used in clinical trials do not support the use of novel therapies in several real-world scenarios involving underrepresented subgroups,such as patients with unpreserved liver function,other comorbid conditions,a history of solid-organ transplantation,autoimmune disorders and those with a high risk of *** present text aims at discussing treatment strategies in these subgroups.

关键词： Eligibility Systemic therapies End-stage Hepatocellular carcinoma

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Combination approaches in hepatocellular carcinoma:How systemic treatment can benefit candidates to locoregional modalities

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World Journal of gastroenterology 2022年第28期28卷 3573-3585页

作者： leonardo gomes da fonseca Raphael L C Araujo Department of Medical Oncology Instituto do Cancer do Estado de Sao PauloUniversity of Sao PauloSão Paulo 01246-000São PauloBrazil Hospital e Maternidade Brasil-Rede D'Or São Luiz Santo André09030-590São PauloBrazil Department of Digestive Surgery Escola Paulista de Medicina-UNIFESPSão Paulo 04023-062São PauloBrazil

The management of hepatocellular carcinoma(HCC)is challenging because most patients have underlying cirrhosis,and the treatment provides,historically,a limited impact on the natural history of patients with advanced-stage ***,recurrence rates are high for those patients who receive local and locoregional modalities,such as surgical(resection and transplantation)or imageguided(ablation and intra-arterial)*** research has led to new concepts that are reshaping the current clinical *** advancements were achieved in the understanding of the hallmarks that drive *** has primed a successful incorporation of novel agents with different targets,such as anti-angiogenic drugs,targeted-therapies,and immune-checkpoint *** clinical trials have proven efficacy of systemic agents in advanced stage disease,there is no conclusive evidence to support their use in combination with loco-regional *** novel local modalities are being incorporated(e.g.,radioembolization,microwave ablation,and irreversible electroporation),emerging data indicate that locoregional treatments may induce tumor microenvironment changes,such as hyperexpression of growth factors,release of tumor antigens,infiltration of cytotoxic lymphocytes,and modulation of adaptative and innate immune *** trials that evaluated the use of antiangiogenic drugs in the adjuvant setting after ablation or chemoembolization fail to demonstrate a substantial *** efforts are directed to investigate the role of immunotherapy-based regimens in this *** present review aims to describe the current landscape of systemic and locoregional treatments for HCC,present evidence to support combination approaches,and address future perspectives.

关键词： Liver cancer Hepatocellular carcinoma Immunotherapy Systemic therapy Ablation Embolization

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Why Sustainable Porous Carbon Should be Further Explored as Radar-Absorbing Material? A Comparative Study with Different Nanostructured Carbons

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Journal of Renewable Materials 2024年第10期12卷 1639-1659页

作者： Alan F.N.Boss Manuella g.C.Munhoz gisele Amaral-Labat Rodrigo g.A.Lima leonardo I.Medeiros Nila C.F.L.Medeiros Beatriz C.S.fonseca Flavia L.Braghiroli guilherme F.B.Lenz e Silva Department of Metallurgical and Materials Engineering University of de São PauloAvenida Mello MoraesCidade UniversitáriaSão PauloSP 05508-030Brazil Coordination of Applied Research and Technological Development National Institute for Space ResearchAvenida dos AstronautasJardim da GranjaSão Josédos CamposSP 12227-010Brazil Department of Exact and Technological Sciences Santa Cruz State UniversityRodovia Jorge Amadokm16IlhéusBA 45662900Brazil Institut de recherche sur les forêts Universitédu Québec en Abitibi-TémiscamingueRouyn-Noranda445 Bd de l’UniversitéRouyn-NorandaQC J9X 5E4Canada

Radar Absorbing Materials(RAM)are a class of composites that can attenuate incident electromagnetic waves to avoid radar *** carbon allotropes that have the potential to be used as RAM are either carbon nano-tubes(CNTs),graphene,carbon black(CB)and ultimately,sustainable porous carbon(SPC).Here,black wattle bark waste(following tannin extraction)was used as a sustainable source to produce SPC made from biomass *** was characterized and used as afiller for a silicone rubber matrix to produce aflexible *** elec-tromagnetic performance of this composite was compared with composites made with commercial CB and CNT through reflection loss(RL),where-10 dB is equivalent to 90%of *** composites were evaluated in single-layer,double-layer,and as radar absorbing structures(RAS)with the aim of improving their effective absorption bandwidth(EAB)performances and a reduction in *** CNT composite presented a RL of-26.85 dB at 10.89 gHz and an EAB of 2.6 gHz with a 1.9 mm thickness,while the double-layer structures using CNT and SPC provided a RL of-19.74 dB at 10.75 gHz and an EAB of 2.51 ***,the double-layer structures are~42%cheaper than the composite using only CNT since less material is ***,the largest EAB was achieved with a RAS using SPC,reaching~2.8 gHz and a RL of-49.09 dB at 10.4 ***,SPC made of black wattle bark waste can be a competitive,alternative material for use as RAM and RAS since it is cheaper,sustainable,and suitable for daily life uses such as absorbers for anechoic chambers,sensors,and elec-tromagnetic interference shields for electronics,wallets,vehicles,and others.

关键词： Microwave absorption material tannin waste dielectric constant carbon composite reflectivity

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Collagen membrane functionalized with magnesium oxide via room-temperature atomic layer deposition promotes osteopromotive and antimicrobial properties

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Bioactive Materials 2023年第12期30卷 46-61页

作者： Soumya Saha Raphael Cavalcante Costa Mirela Caroline Silva Joao Matheus fonseca-Santos Lin Chen Abhijit H.Phakatkar Harshdeep Bhatia leonardo P.Faverani Valentim A.R.Barao Tolou Shokuhfar Cortino Sukotjo Christos Takoudis Department of Biomedical Engineering University of Illinois ChicagoChicagoUSA Department of Prosthodontics and Periodontology Piracicaba Dental SchoolUniversity of Campinas(UNICAMP)PiracicabaSao PauloBrazil Department of Diagnosis and Surgery Division of Oral and Maxillofacial Surgery and ImplantologySao Paulo State University(UNESP)School of DentistryAraçatubaSao PauloBrazil Department of Periodontics Center for Wound Healing and Tissue RegenerationCollege of DentistryUniversity of Illinois ChicagoChicagoUSA Department of Chemical Engineering University of Illinois ChicagoChicagoUSA Department of Restorative Dentistry University of Illinois Chicago College of DentistryChicagoUSA

Artificial bone grafting materials such as collagen are gaining interest due to the ease of production and ***,collagen must be supplemented with additional coating materials for improved ***,we report room-temperature atomic layer deposition(ALD)of MgO,a novel method to coat collagen membranes with *** techniques such as X-ray photoelectron spectroscopy,Raman spectroscopy,and electron beam dispersion mapping confirm the chemical nature of the *** electron and atomic force microscopies show the surface topography and morphology of the collagen fibers were not altered during the ALD of *** release of magnesium ions promotes bone growth,and we show the deposited MgO film leaches trace amounts of Mg when incubated in phosphate-buffered saline at 37◦*** coated collagen membrane had a superhydrophilic surface immediately after the deposition of *** film was not toxic to human cells and demonstrated antibacterial properties against bacterial ***,in vivo studies performed on calvaria rats showed MgO-coated membranes(200 and 500 ALD)elicit a higher inflammatory response,leading to an increase in angiogenesis and a greater bone formation,mainly for Col-MgO500,compared to uncoated *** on the characterization of the MgO film and in vitro and in vivo data,the MgO-coated collagen membranes are excellent candidates for guided bone regeneration.

关键词： coating magnesium atomic

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Multi-omics Analysis of Young Portulaca oleracea ***’Responses to High NaCl Doses Reveals Insights into Pathways and genes Responsive to Salinity Stress in this Halophyte Species

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Phenomics 2023年第1期3卷 1-21页

作者： Vivianny Nayse Belo Silva Thalliton Luiz Carvalho da Silva Thalita Massaro Malheiros Ferreira Jorge Candido Rodrigues Neto AndréPereira Leão JoséAntônio de Aquino Ribeiro Patrícia Verardi Abdelnur leonardo fonseca Valadares Carlos Antônio Ferreira de Sousa Manoel Teixeira Souza Júnior graduate Program of Plant Biotechnology Federal University of LavrasCP 3037LavrasMG 37200-000Brazil Institute of Chemistry Federal University of GoiásCampus SamambaiaGoiâniaGO 74690‐900Brazil Brazilian Agricultural Research Corporation Embrapa Mid-NorthTeresinaPI 64008-780Brazil Brazilian Agricultural Research Corporation Embrapa AgroenergyBrasíliaDF 70770‐901Brazil

Soil salinity is among the abiotic stressors that threaten agriculture the most,and purslane(Portulaca oleracea L.)is a dicot species adapted to inland salt desert and saline habitats that hyper accumulates salt and has high phytoremediation *** researchers consider purslane a suitable model species to study the mechanisms of plant tolerance to drought and salt ***,a robust salinity stress protocol was developed and used to characterize the morphophysiological responses of young purslane plants to salinity stress;then,leaf tissue underwent characterization by distinct omics platforms to gain further insights into its response to very high salinity *** salinity stress protocol did generate different levels of stress by gradients of electrical conductivity at field capacity and water potential in the saturation extract of the substrate,and the morphological parameters indicated three distinct stress *** expected from a halophyte species,these plants remained alive under very high levels of salinity stress,showing salt crystal-like structures constituted mainly by Na^(+),Cl^(−),and K^(+)on and around closed stomata.A comprehensive and large-scale metabolome and transcriptome single and integrated analyses were then employed using leaf *** multi-omics integration(MOI)system analysis led to a data-set of 51 metabolic pathways with at least one enzyme and one metabolite differentially expressed due to salinity *** data sets(of genes and metabolites)are valuable for future studies aimed to deepen our knowledge on the mechanisms behind the high tolerance of this species to salinity *** conclusion,besides showing that this species applies salt exclusion already in young plants to support very high levels of salinity stress,the initial analysis of metabolites and transcripts data sets already give some insights into other salt tolerance mechanisms used by this species to support high levels of salinity stress.

关键词： Purslane RNA-Seq Chemometrics High-resolution mass spectrometry Abiotic stress Multi-omics integration

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Laparoscopic liver resection:Experience based guidelines

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World Journal of gastrointestinal Surgery 2016年第1期8卷 5-26页

作者： fabricio ferreira coelho jaime arthur pirola kruger gilton marques fonseca raphael leonardo cunha araújo vagner birk jeismann marcos vinícius perini renato micelli lupinacci ivan cecconello paulo herman liver surgery unit department of gastroenterologyuniversity of sao paulo medical schoolSao PauloCEP 05403-900Brazil austin health Department of SurgeryUniversity of MelbourneHeidelbergVIC 3084Australia service de chirurgie digestive viscérale et endocrinienne groupe hospitalier diaconesses-croix saint simon75020 ParisFrance

Laparoscopic liver resection(LLR) has been progressively developed along the past two decades. Despite initial skepticism, improved operative results made laparoscopic approach incorporated to surgical practice and operations increased in frequency and complexity. Evidence supporting LLR comes from case-series, comparative studies and meta-analysis. Despite lack of level 1 evidence, the body of literature is stronger and existing data confirms the safety, feasibility and benefits of laparoscopic approach when compared to open resection. Indications for LLR do not differ from those for open surgery. They include benign and malignant(both primary and metastatic) tumors and living donor liver harvesting. Currently, resection of lesions located on anterolateral segments and left lateral sectionectomy are performed systematically by laparoscopy in hepatobiliary specialized centers. Resection of lesions located on posterosuperior segments(1, 4a, 7, 8) and major liver resections were shown to be feasible but remain technically demanding procedures, which should be reserved to experienced surgeons. Hand-assisted and laparoscopy-assisted procedures appeared to increase the indications of minimally invasive liver surgery and are useful strategies applied to difficult and major resections. LLR proved to be safe for malignant lesions and offers some short-term advantages over open resection. Oncological results including resection margin status and long-term survival were not inferior to open resection. At present, surgical community expects high quality studies to base the already perceived better outcomes achieved by laparoscopy in major centers' practice. Continuous surgical training, as well as new technologies should augment the application of lap-aroscopic liver surgery. Future applicability of new technologies such as robot assistance and image-guided surgery is still under investigation.

关键词： Minimally invasive surgery Laparoscopicsurgery Hand-assisted laparoscopy Liver neoplasm Liver cirrhosis Living donor Liver Hepatectomy Livertransplantation

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血浆和(或)酵母提取物对7-63日龄仔猪生长性能和肠道形态的影响

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饲料研究 2014年第9期37卷 21-27页

作者： Leandro César Milagres Rigueira Maria Cristina Thomaz Dalton César Milagres Rigueira leonardo Augusto fonseca Pascoal Alessandro Borges Amorim Fábio Enrique Lemos Budio 周小辉骆明霞严书林

研究旨在评估在7～63日龄仔猪日粮中添加血浆和（或）酵母提取物对仔猪日增质量、日采食量和饲料转化率及肠道形态的影响。试验采用288头体质量为（2．57±0．05）kg的7日龄仔猪，按照日粮差别随机分为4组，每组6个重复，每重复12头仔... 详细信息

研究旨在评估在7～63日龄仔猪日粮中添加血浆和（或）酵母提取物对仔猪日增质量、日采食量和饲料转化率及肠道形态的影响。试验采用288头体质量为（2．57±0．05）kg的7日龄仔猪，按照日粮差别随机分为4组，每组6个重复，每重复12头仔猪。试验预备期I（7～21日龄）、预备期II（22—35日龄）及第1阶段（36～49日龄）各组日粮为对照组（CD组），不添加血浆或酵母提取物；血浆组（PL组），添加6％、4％和2％血浆；酵母提取物组（YE组），添加6％、4％和2％酵母提取物；血浆＋酵母提取物组（PL＋YE组），血浆和酵母提取物分别添加3％、2％和1％。第1I阶段（50—63日龄）所有仔猪饲喂相同的饲料。7～21和7～28日龄没有观察到生长性能的差别，但是第7天一第35天PL＋YE组的日增质量有优势（CD、PL、YE和PL＋YE组的日增质量分别为268、278、271和288g）。观察7～49及7～63日龄发现，PL＋YE组仔猪的日增质量（分别为330和519g）和日采食量（分别为307和647g）都比CD组的日增质量（分别为295和486g）和日采食量（分别为266和594g）要高。不同组间的肠道形态没有显著差异（P〉0．05）。试验结果表明，血浆和酵母提取物提高7～63日龄的仔猪日增质量，但是没有影响到仔猪的肠道形态。

关键词：饲料转化率采食量仔猪肠绒毛增质量

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应用高强度钢材实现工业厂房减量化设计的实例

应用高强度钢材实现工业厂房减量化设计的实例

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'2012中国钢结构行业大会

作者： leonardo Silvestre Roberval Pimenta Marcos Nogueira Luci Queiroz Hernane Salles Alexandre Jordao Rodolfo Ribeiro Mariana Pimenta Juliano Conceio leonardo Rocha Felipe Buratto Eduardo fonseca 王厚昕巴西矿冶公司(CBMM)技术部

本文以CBMM在巴西Araxa的工厂作为实例,介绍了采用微合金化钢进行工业厂房减量化设计的情况。该厂房的结构大多使用了ASTM A572微合金化钢,而不是传统的ASTM A36碳锰钢。本文从冶金角度对这两类钢各自的微观组织以及力学性能进行了评定... 详细信息

本文以CBMM在巴西Araxa的工厂作为实例,介绍了采用微合金化钢进行工业厂房减量化设计的情况。该厂房的结构大多使用了ASTM A572微合金化钢,而不是传统的ASTM A36碳锰钢。本文从冶金角度对这两类钢各自的微观组织以及力学性能进行了评定。由于铌同时提高了钢材的强度和韧性,该项目因含Nb高性能钢而节约了22%钢材消耗量。

关键词：工业建筑铌微合金化减量化设计高强度钢

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