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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

Assessing the prognosis of cirrhotic patients in the intensive care unit:What we know and what we need to know better

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World Journal of Hepatology 2021年第10期13卷 1341-1350页

作者： Fernando da silveira Pedro H R soares luana Q Marchesan Roberto s A da fonseca Wagner l Nedel Programa de Pos-Graduacao em Pneumologia Universidade Federal do Rio Grande do SulPorto Alegre 91430835Brazil Intensive Care Unit Grupo Hospitalar ConceiçãoPorto Alegre 91430835Brazil Programa de Pos-Graduacao em Neurociencias Universidade Federal do Rio Grande do SulPorto Alegre 91430835Brazil Programa de Pos-Graduacao em Ciencias da saude Universidade Federal de Santa MariaSanta Maria 97105900Brazil Programa de Pos-Graduacao em Bioquimica Universidade Federal do Rio Grande do SulPorto Alegre 91430835Brazil

Critically ill cirrhotic patients have high in-hospital mortality and utilize significant health care resources as a consequence of the need for multiorgan *** this fact,their mortality has decreased in recent decades due to improved care of critically ill ***-on-chronic liver failure(AClF),sepsis and elevated hepatic scores are associated with increased mortality in this population,especially among those not eligible for liver *** score is superior to another in the prognostic assessment of these patients,and both liver-specific and intensive care unit-specific scores have satisfactory predictive *** sequential assessment of the scores,especially the sequential Organ Failure Assessment(sOFA)and Chronic liver Failure Consortium(ClIF)-sOFA scores,may be useful as an auxiliary tool in the decision-making process regarding the benefits of maintaining supportive therapies in this population.A ClIF-AClF>70 at admission or at day 3 was associated with a poor prognosis,as well as sOFA score>19 at baseline or increasing sOFA score>*** studies addressing the prognostic assessment of these patients are necessary.

关键词： Cirrhosis Extrahepatic organ failure Organ replacement therapy Mortality Prognostic scores Chronic liver Failure Consortium-sequential Organ Failure Assessment sequential Organ Failure Assessment Model for End-stage liver Disease

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

The preventive and therapeutic potential of native Brazilian fruits on colorectal cancer

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Food Bioscience 2022年第2期46卷 55-72页

作者： Roberto de Paula do Nascimento lívia Mateus Reguengo Ana Paula da fonseca Machado Mario Roberto Marostica Junior University of Campinas School of Food EngineeringMonteiro Lobato Street 8013083-862CampinasS˜ao Paulo stateBrazil

In the last years,colorectal cancer(CRC)has been increasing substantially in developing *** the consumption of fat and meat have been linked with increased CRC risk,fruits intake can be *** addition,since CRC’s chemotherapy may be accompanied with adverse effects,natural plant products have been postulated as alternative or complementary therapeutic *** fruits are rich sources of bioactive compounds,mainly phenolic compounds,with antioxidant,anti-inflammatory,and anticancer benefits,thus,future candidates for CRC ***,this narrative review aims to present and discuss the potential of native Brazilian fruits(e.g.,açaí,cocoa,jaboticaba,passionfruit)on *** studies performed from 2001 to present were ***-rich powders and extracts from Brazilian fruits are the most promising products for CRC *** with açaí(Euterpe oleracea)and cocoa(Theobroma cacao)are more numerous and their effects on CRC models in vitro and in vivo are demonstrated with more complexity in terms of molecular *** main signaling pathways modulated by the effects of native Brazilian fruits,so far studied on CRC,are associated with:***(B-cell lymphoma 2-and caspase 3-related proteins),***(pro-inflammatory interleukins and enzymes),and *** stress(antioxidant enzymes).In addition,adhesion molecules and nuclear factor kappa B have been shown to be downregulated,which can interfere positively in several cellular processes,including proliferation,angiogenesis,and *** investigation of signaling pathways of great relevance for CRC initiation and progression is still necessary.

关键词： Anthocyanin Bioactive compound Carcinogenesis Euterpe oleracea Phenolic compound Theobroma cacao

Turning the corner from observation to intervention in human genetics

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Journal of Genetics and Genomics 2018年第2期45卷 57-59页

作者： david l.nelson Department of Molecular and Human Genetics Baylor College of Medicine Jan and Dan Duncan Neurological Research Institute

In the early 1990s,shortly after we identified the genetic defect in FMR1 that results in fragile X syndrome（Verkerk et al.,1991）,I attended a conference sponsored by the Us National Fragile X *** biannual meeting m... 详细信息

关键词： Turning the corner from observation to intervention in human genetics

Retention of eucalyptus harvest residues reduces soil compaction caused by deep subsoiling

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Journal of Forestry Research 2022年第2期33卷 643-651页

作者： Raphael Oliveira de Melo AymbiréAngeletti da fonseca Nairam Félix de Barros Raphael Bragança Alves Fernandes Rafael da silva Teixeira Iago Nery Melo Ricardo Previdente Martins soil science Department Universidade Federal de ViçosaViçosaMinas GeraisBrazil BRACEll Company AlagoinhasBahiaBrazil

Eucalyptus harvesting,forwarding and soil tillage operations are among the main causes for compaction of forest soils,with potential impacts on *** concern is especially important in areas with soils that are naturally compacted(fragipans and duripans).In these soils,tillage operations include the use of subsoilers that can reach depths of more than one meter and require heavy tractors that exert high pressure on the *** of the ways to try to minimize the effect of this compaction is by retaining harvest *** objective of this study was to evaluate the impacts of eucalyptus harvesting on soil physical attributes,as well as to determine the potential of different types of residue management to reduce compaction from the soil tillage *** experiments were conducted in the same area with a Yellow *** the first experiment,compaction caused by mechanized harvesting with harvester+forwarder was *** the second experiment,different managements of harvest residues were examined as potential modifiers of soil compaction during tillage for new *** this,three managements systems were tested:(1)retention of all harvest residues and litter from the previous rotation(HR+l),(2)retention of litter from the previous rotation(l),and(3)removal of harvest residues and litter from the previous rotation(WR).Before and after harvest,sampling was carried out in the planting rows and inter-rows,and after tillage,samples were collected in the traffic line of the subsoiler-tractor *** both experiments,undisturbed soil samples were collected from the center of the 0-10,10-20,20-40,40-60,and 60-100 cm layers to determine soil density and total *** each period and site of evaluation,mechanical resistance to penetration up to the 60-cm depth was also *** harvesting operation increased soil density at 0-10 and 60-100 cm depths only in the *** of harvest residues and litter(HR+l)after harvesting avoi

关键词： soil penetration resistance Harvester+forwarder soil tillage soil density Cohesive soils

Discharge-stage Relationship on Urban streams Evaluated at UsGs Gauging stations,***,Missouri

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Journal of Earth science 2020年第6期31卷 1133-1141页

作者： Robert E.Criss david l.nelson Department of Earth and Planetary sciences Washington UniversitySt.Louis MO 63130USA Columbia Cir Pasadena CA 91105USA

Extensive UsGs data tables and detailed,1 m2 li daR surveys are used to determine the optimal power n that relates discharge(Q)to stage(h*)above channel bottom(ho)at 39 gauging stations on small streams in the ***,Missouri area,all of which have catchments of 0.6 to 220 *** different methodologies are employed to determine both n and ho:(1)optimizing linearity in a plot of Q1/n *** stage(hl)using UsGs field measurements at each site;(2)optimizing linearity in a plot of Q1/n *** using UsGs rating tables at each site;(3)a mathematical inverse method applied to the same UsGs rating tables;(4)use of li daR data on channel geometry to determine the power dependences of channel area A and hydraulic radius H on h*,combined with the Manning and rational equations to predict *** these methods,only methods 2 and 3 compare favorably,and these values compare poorly with Method 1 based on field data,and with method 4 based on theoretical and empirical *** Method 4 is predictive,it provides a useful alternative to methods 1–3 that are based on UsGs field measurements,which are heavily weighted toward low *** conclude that the apparent values of n in the UsGs rating tables are systematically too low for small streams.

关键词： stream gauging li daR topography urban flooding discharge hydrology

Basic density, extractive content and moisture sorption properties of Pinus pinaster wood infected with the pinewood nematode, Bursaphelenchus xylophilus

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Journal of Forestry Research 2015年第1期26卷 233-240页

作者： Valeria Reva luís fonseca José l.lousada Isabel Abrantes António R.Figueiredo Domingos X.Viegas Centre of Forest Fire studies Association for the Development of Industrial Aerodynamics(CEIF/ADAI) Rua Pedro Hispano CFE-Centre for Functional Ecology Department of Life SciencesUniversity of Coimbra Centre for Research and Technology of Agro-Environment Biological sciences(CITAB) UTADQuinta dos Prados Apartado

The pinewood nematode（PWN）, Bursaphelenchus xylophilus, has become one of the most severe threats to pine forest worldwide. Nematodes, migrating through resin canals and feeding on the living cells, induce rapid metabolic changes in ray parenchyma cells, create cavitation areas, decrease xylem water content and oleoresin exudation, and cause necrosis of parenchyma and cambial cells. This study focused on the impact of PWN infection on technological parameters of wood and evaluated the impact of anatomic and biochemical incidences of tree defense reactions on basic density, extractive content and moisture sorption properties of Pinus pinaster *** of infected and uninfected wood were *** presence of nematodes reduced wood basic density by2 % and decreased the total content of extractives in infected wood as compared with uninfected（5.98 and8.90 % of dry wood mass, respectively）. Extractives in infected trees had inverse distribution along the trunk as compared with uninfected trees. The adsorption isotherms for infected and uninfected wood had similar *** recorded differences（some statistically significant） in the equilibrium moisture content of infected and uninfected wood under varying environmental conditions. Despite the verified differences in wood basic density, extractive content and moisture sorption properties, the overall conclusion is that the PWN had a slight impact on these characteristics of wood.

关键词： Pinewood nematode Wood density Extractives Equilibrium moisture content Economic impact

An oxygenating colloidal bioink for the engineering of biomimetic tissue constructs

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Bio-Design and Manufacturing 2024年第3期7卷 240-261页

作者： seol-Ha Jeong Jarno Hiemstra Patrick V.Blokzijl Rebeca damian-Ferrara danilo Martins dos santos Jéssica H.l.da fonseca Min-Ho Kang Jihyun Kim Dilara Yilmaz-Aykut Mei l.l.Cham-Pérez Jeroen leijten su Ryon shin Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02139USA leijten lab Department of Developmental BioEngineeringFaculty of Science and TechnologyTechnical Medical CentreUniversity of TwenteDrienerlolaan 57522 NB EnschedeThe Netherlands Nanotechnology National laboratory for Agriculture(lNNA) Embrapa InstrumentaçãoSao CarlosSao Paulo 13560-970Brazil Department of Biomedical-Chemical Engineering The Catholic University of Korea43 Jibong-roBucheon-siGyeonggi-do 14662Republic of Korea Department of Biotechnology The Catholic University of Korea43 Jibong-roBucheon-siGyeonggi-do 14662Republic of Korea

Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural *** in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted *** oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain *** study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with *** report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide ***,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase *** study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release ***,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal *** showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new *** findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated *** work thereby offers a promising avenue for the development of functional tissues with e

关键词： 3D bioprinting Bioink Colloidal gels Extrusion printing Oxygen-generating microparticle