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| 1 | Specific CD8^+ T cell response immunotherapy for hepatocellular carcinoma and viral hepatitis显示文摘Hepatocellular carcinoma(HCC), chronic hepatitis B(CHB) and chronic hepatitis C(CHC) are characterized by exhaustion of the specific CD8^+ T cell response. This process involves enhancement of negative costimulatory molecules, such as programmed cell death protein-1(PD-1), cytotoxic T-lymphocyte antigen-4(CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8^+ T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4(tremelimumab and ipilimumab) and PD-1(nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway. | Elia Moreno-Cubero Juan-Ramón Larrubia | 2016 | World Journal of Gastroenterology2016，22，28： | 13 |
| 2 | Autophagy in liver diseases显示文摘Autophagy is the liver cell energy recycling system regulating a variety of homeostatic mechanisms.Damaged organelles,lipids and proteins are degraded in the lysosomes and their elements are re-used by the cell.Investigations on autophagy have led to the award of two Nobel Prizes and a health of important reports.In this review we describe the fundamental functions of autophagy in the liver including new data on the regulation of autophagy.Moreover we emphasize the fact that autophagy acts like a two edge sword in many occasions with the most prominent paradigm being its involvement in the initiation and progress of hepatocellular carcinoma.We also focused to the implication of autophagy and its specialized forms of lipophagy and mitophagy in the pathogenesis of various liver diseases.We analyzed autophagy not only in well studied diseases,like alcoholic and nonalcoholic fatty liver and liver fibrosis but also in viral hepatitis,biliary diseases,autoimmune hepatitis and rare diseases including inherited metabolic diseases and also acetaminophene hepatotoxicity.We also stressed the different consequences that activation or impairment of autophagy may have in hepatocytes as opposed to Kupffer cells,sinusoidal endothelial cells or hepatic stellate cells.Finally,we analyzed the limited clinical data compared to the extensive experimental evidence and the possible future therapeutic interventions based on autophagy manipulation. | Elias Kouroumalis Argryro Voumvouraki Aikaterini Augoustaki Dimitrios N Samonakis | 2021 | World Journal of Hepatology2021，13，1： | 7 |
| 3 | Systemic treatment for hepatocellular carcinoma:Still unmet expectations显示文摘Many patients with hepatocellular carcinoma(HCC) are diagnosed in an advanced stage, so they cannot be offered the option of curative treatments. The results of systemic chemotherapy are unsatisfactory and this has led to molecular targeted approaches.HCC develops in chronically damaged tissue due to cirrhosis in most patients. Several different cell types and molecules constitute a unique microenvironment in the liver, which has significant implications in tumor development and invasion. This, together with genome instability, contributes to a significant heterogeneity which is further enhanced by the molecular differences of the underlying causes. New classifications based on genetic characteristics of the tissue microenvironment have been proposed and key carcinogenic signaling pathways have been described. Tumor and adjacent tissue profiling seem biologically promising, but have not yet been translated into clinical settings. The encouraging first results with molecular- genetic signatures should be validated and clinically applicable. A more personalized approach to modern management of HCC is urgently needed. | Dimitrios N Samonakis Elias A Kouroumalis | 2017 | World Journal of Hepatology2017，9，2： | 6 |
| 4 | Is it possible to stop nucleos(t)ide analogue treatment in chronic hepatitis B patients?显示文摘Chronic hepatitis B(CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue(NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus(HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen(HBs Ag), but this is hardly ever achieved. Therefore, indefinite treatment is usually required. Many different studies have evaluated NA therapy discontinuation after several years of NA treatment and before HBs Ag loss. The results have indicated that the majority of patients can remain off therapy, with some even reaching HBs Ag seroconversion. Fortunately, this strategy has proved to be safe, but it is essential to consider the risk of liver damage and other comorbidities and to ensure aclose follow-up of the candidates before considering this strategy. Unanswered questions remain, namely in which patients could this strategy be effective and what is the optimal time point at which to perform it. To solve this enigma, we should keep in mind that the outcome will ultimately depend on the equilibrium between HBV and the host's immune system. Viral parameters that have been described as good predictors of response in HBe Ag(+) cases, have proven useless in HBe Ag(-) ones. Since antiviral immunity plays an essential role in the control of HBV infection, we sought to review and explain potential immunological biomarkers to predict safe NA discontinuation in both groups. | Elia Moreno-Cubero Robert T Sánchez del Arco Julia Pena-Asensio Eduardo Sanz de Villalobos Joaquín Míquel Juan Ramón Larrubia | 2018 | World Journal of Gastroenterology2018，24，17： | 5 |
| 5 | Management of oligometastatic non-small cell lung cancer patients:Current controversies and future directions显示文摘Oligometastatic non-small cell lung cancer(NSCLC)describes an intermediate stage of NSCLC between localized and widely-disseminated disease.This stage of NSCLC is characterized by a limited number of metastases and a more indolent tumor biology.Currently,the management of oligometastatic NSCLC involves radical treatment(radiotherapy or surgery)that targets the metastatic lesions and the primary tumor to achieve disease control.This approach offers the potential to achieve prolonged survival in patients who,in the past,would have only received palliative measures.The optimal therapeutic strategies for the different scenarios of oligometastatic disease(intracranial vs extracranial disease,synchronous vs metachronous)remain undefined.Given the lack of head-to-head studies comparing radiotherapy to surgery in these patients,the decision to apply surgery or radiotherapy(with or without systemic treatment)must be based on prognostic factors that allow us to classify patients.This classification will allow us to select the most appropriate therapeutic strategy on an individualized basis.In the future,the molecular or microRNA profiles will likely improve the treatment selection process.The objective of the present article is to review the most relevant scientific evidence on the management of patients with oligometastatic NSCLC,focusing on the role of radiotherapy and surgery.We also discuss areas of controversy and future directions. | Felipe Counago Javier Luna Luis Leonardo Guerrero Blanca Vaquero María Cecilia Guillén-Sacoto Teresa González-Merino Begona Taboada Verónica Díaz Belén Rubio-Viqueira Ana Aurora Díaz-Gavela Francisco JoséMarcos Elia del Cerro | 2019 | World Journal of Clinical Oncology2019，10，10： | 5 |
| 6 | Clinical outcomes of compensated and decompensated cirrhosis: A long term study显示文摘AIM: To study these characteristics and prognostic patterns in a Greek patient population.METHODS: We analyzed a large cohort of cirrhotic patients referred to the department of Gastroenterology and Hepatology and the outpatient clinics of this tertiary hospital, between 1991 and 2008. We included patients with established cirrhosis, either compensated or decompensated, and further decompensation episodes were registered. A data base was maintained and updated prospectively throughout the study period.We analyzed differences in cirrhosis aetiology, time to and mode of decompensation, hepatocellular carcinoma(HCC) occurrence and ultimately patient survival.RESULTS: Five hundreds and twenty-two patients with median age 67(range, 29-91) years and average follow up 9 years-10 mo(range, 1-206 mo) were studied. Commonest aetiology was hepatitis C virus(HCV, 41%) followed by alcohol(31%). The median survival time in compensated cirrhotics was 115 mo(95%CI: 95-133), whereas in decompensated patients was 55 mo(95%CI: 36-75). HCV patients survived longer while HBV patients had over twice the risk of death of HCV patients. The median time to decompensation was 65 mo(95%CI: 51-79), with alcoholics having the highest risk(RR = 2.1 vs HCV patients). Hepatitis B virus(HBV) patients had the highest risk of HCC, alcoholics the lowest. Leading causes of death: liver failure, hepatorenal syndrome, sepsis and HCC progression. CONCLUSION: Cirrhosis aetiology and decompensation at presentation were predictors of survival. Alcoholics had the highest decompensation risk, HBV cirrhotics the highest risk of HCC and HCV cirrhotics the highest decompensation-free time. | Dimitrios N Samonakis Mairi Koulentaki Constantina Coucoutsi Aikaterini Augoustaki Chryssavgi Baritaki Emmanuel Digenakis Nikolaos Papiamonis Maria Fragaki Erminia Matrella Elias A Kouroumalis Maria Tzardi | 2014 | World Journal of Hepatology2014，6，7： | 4 |
| 7 | Second-look surgery plus hyperthermic intraperitoneal chemotherapy for patients with colorectal cancer at high risk of peritoneal carcinomatosis:Does it really save lives?显示文摘The treatment of peritoneal carcinomatosis (PC) of colorectal origin with cytoreductive surgery(CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has a 5-year recurrence-free or cure rate of at least 16%, so it is no longer labeled as a fatal disease, and offers prolonged survival for patients with a low peritoneal carcinomatosis index. Metachronous PC of colorectal origin is so predictable that there is a model which has been used to successfully determine the individual risk of each patient. Patients at risk are clearly identified; those with the highest risk have small peritoneal nodules present in the first surgery (70% probability of developing PC), ovarian metastases(60%), perforated tumor onset or intraoperative tumor rupture(50%). Current clinical, biological and imaging techniques still lack sufficient sensitivity to diagnose PC in its initial stages, when CRS plus HIPEC has a greater impact and a higher cure rate. Second-look surgery with HIPEC or prophylactic HIPEC at the time of the first intervention have been proposed as means of preventing and/or anticipating clinical or radiological relapse in at-risk patients. Both techniques have shown a significant decrease in peritoneal relapses and should be considered essential weapons in the management of colorectal cancer. | Delia Cortes-Guiral Dominique Elias Pedro Antonio Cascales-Campos Alfredo Badía Yébenes Ismael Guijo Castellano Ana Isabel León Carbonero JoséIgnacio Martín Valadés Jesus Garcia-Foncillas Damian Garcia-Olmo | 2017 | World Journal of Gastroenterology2017，23，3： | 3 |
| 8 | Hepatitis C virus-specific cytotoxic T cell response restoration after treatment-induced hepatitis C virus control显示文摘Hepatitis C virus(HCV)-specific cytotoxic T cell(CTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onset, being unable to get rid of HCV. The role of this response in contributing to sustained viral response(SVR) after anti-HCV is controversial. Recent studies show that after successful interferon-based anti-HCV treatment, HCV traces are still detectable and this correlates with a peak of HCV-specific CTL response activation, probably responsible for maintaining SVR by subsequent complete HCV clearing. Moreover, SVR patients' serum is still able to induce HCV infection in na?ve chimpanzees, suggesting that the infection could be under the control of the immune system after a successful treatment, being transmissible in absence of this adaptive response. At least theoretically, treatmentinduced viral load decrease could allow an effective HCV-specific CTL response reestablishment. This effect has been recently described with anti-HCV interferonfree regimes, based on direct-acting antivirals. Nevertheless, this is to some extent controversial with interferon-based therapies, due to the detrimental immunoregulatory α-interferon effect on T cells. Moreover, HCV-specific CTL response features during anti-HCV treatment could be a predictive factor of SVR that could have clinical implications in patient management. In this review, the recent knowledge about the role of HCV-specific CTL response in the development of SVR after anti-HCV treatment is discussed. | Juan-Ramón Larrubia Elia Moreno-Cubero Joaquín Miquel Eduardo Sanz-de-Villalobos | 2015 | World Journal of Gastroenterology2015，21，12： | 3 |
| 9 | TIPS for Budd-Chiari Syndrome: Long-Term Results and Prognostics Factors in 124 Patients显示文摘 | Juan Carlos Garcia–Pagán Mathis Heydtmann Sebastian Raffa Aurélie Plessier Sarwa Murad Federica Fabris Giovanni Vizzini Juan Gonzales Abraldes Simon Olliff Antonio Nicolini Angelo Luca Massimo Primignani Harry L.A. Janssen Dominique Valla Elwyn Elias Jaum | 2008 | Gastroenterology2008，，3： | 3 |
| 10 | Complex causes and consequences of rangeland greening in South America -multiple interacting natural and anthropogenic drivers and simultaneous ecosystem degradation and recovery trends显示文摘Land-surface greening has been reported globally over the past decades.While often seen to represent ecosystem recovery,the impacts on biodiversity and society can also be negative.Greening has been widely reported from rangelands,where drivers and processes are complex due to its high environmental heterogeneity and societal dynamics.Here,we assess the complexity behind greening and assess its links to various drivers in an iconic,heterogeneous rangeland area,the IberáWetlands and surroundings,in Argentina.Time-series satellite imagery over the past 19 years showed overall net greening,but also substantial local browning both in protected and unprotected areas,linking to land use,temporal changes in surface water,fire,and weather.We found substantial woody expansion mainly in the unprotected land,with 37%contributed by tree plantations and the remaining 63%by spontaneous woody expansion,along with widespread transitions from terrestrial land to seasonal surface water.Fire occurrences tended to reduce greening with unprotected areas experiencing widespread and frequent fire.However,protected areas had more browning in unburnt areas than burned areas.Temporal variation in annual precipitation and temperature tended to nonlinearly influence fire occurrences with an interplay of human fire management,further shaping the vegetation greening,pointing to high complexity behind the observed rangeland greening involving interactions among local drivers.Our findings highlight that the observed overall greening is an outcome of multiple trends with clear negative impacts on biodiversity and the local livestock-oriented culture(notably expanding tree plantations)and spontaneous vegetation dynamics,partly involving spontaneous woody expansion.The latter has positive potential for biodiversity and ecosystem services in terms of woodland recovery,but can become negative in such a natural savanna region if expansions develop on a too broad scale,highlighting the importance of ensuring recovery of natural fire and herbivory regimes in protected areas along with sustainable rangeland management elsewhere. | Wang Li Robert Buitenwerf Renata Nicora Chequín Javier Elias Florentín Roberto Manuel Salas Julia Carolina Mata Li Wang Zheng Niu Jens-Christian Svenning | 2020 | Geography and Sustainability2020，1，4： | 2 |
| 11 | FRAME: femtosecond videography for atomic and molecular dynamics显示文摘Many important scientific questions in physics,chemistry and biology require effective methodologies to spectroscopically probe ultrafast intra-and inter-atomic/molecular dynamics.However,current methods that extend into the femtosecond regime are capable of only point measurements or single-snapshot visualizations and thus lack the capability to perform ultrafast spectroscopic videography of dynamic single events.Here we present a laser-probe-based method that enables two-dimensional videography at ultrafast timescales(femtosecond and shorter)of single,non-repetitive events.The method is based on superimposing a structural code onto the illumination to encrypt a single event,which is then deciphered in a post-processing step.This coding strategy enables laser probing with arbitrary wavelengths/bandwidths to collect signals with indiscriminate spectral information,thus allowing for ultrafast videography with full spectroscopic capability.To demonstrate the high temporal resolution of our method,we present videography of light propagation with record high 200 femtosecond temporal resolution.The method is widely applicable for studying a multitude of dynamical processes in physics,chemistry and biology over a wide range of time scales.Because the minimum frame separation(temporal resolution)is dictated by only the laser pulse duration,attosecondlaser technology may further increase video rates by several orders of magnitude. | Andreas Ehn Joakim Bood Zheming Li Edouard Berrocal Marcus Aldén Elias Kristensson | 2017 | Light(Science & Applications)2017，6，1： | 2 |
| 12 | Mean platelet volume: a useful marker of inflammatory bowel disease activity显示文摘 | Andreas N Kapsoritakis Michael I Koukourakis Aekaterini Sfiridaki Spiros P Potamianos Maria G Kosmadaki Ioannis E Koutroubakis Elias A Kouroumalis | 2001 | The American Journal of Gastroenterology2001，，3： | 2 |
| 13 | Effect of ausforming on microstructure and hardness of AISI H13 tool steel modified with niobium显示文摘 | Elias C N and Costa Viana C S Da | 1992 | Materials Science and Technology1992，9，： | 1 |
| 14 | Photosensor de- vice based on few-layered WS2 films显示文摘 | Perea-L6pez N Elias A L Berkdemir A | 2013 | Advanced Functional Materials2013，23，44： | 1 |
| 15 | Bounds on the distance two-domination number of a graph 显示文摘 | Sridharan N Subramanian V S A Elias M D | 2002 | Graphs and Combinatorics2002，18，： | 1 |
| 16 | Functional identification of the alveolar edema reabsorption activity of murine tumor necrosis factor-α 显示文摘 | Elia N Tapponnier M Matthay MA | 2003 | Am J Respir Crit Care Med2003，168，8： | 1 |
| 17 | Remote stabilization over fading channels 显示文摘 | ELIA N | 2005 | Systems Control Letters2005，54，3： | 1 |
| 18 | Acceptance sampling: an efficient, accurate method for estimating and optimizing parametric yield 显示文摘 | ELIAS N J | 1994 | IEEE J Sol Sta Circ1994，29，3： | 1 |
| 19 | The ROCK inhibitor Y-27632 improves recovery of human embryonic stem cells after fluorescence-activated cell sorting with multiple cell surface markers显示文摘 | Emre N Vidal JG Elia J | | 0，，08： | 1 |
| 20 | Stabilization of linear systems with limited information显示文摘 | Elia N Mitter S K | | 0，，09： | 1 |
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