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SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation

Cancer Communications 2024年第3期44卷 384-407页

作者： Shiyu Zhang Xing Jia Haojiang Dai Xingxin Zhu Wenfeng Song Suchen Bian Hao Wu Shinuo Chen Yangbo Tang Junran Chen Cheng Jin Mengqiao Zhou Haiyang Xie Shusen Zheng Penghong Song Division of hepatobiliary and pancreatic surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP.R.China National Health Commission Key Laboratory of Combined Multi-organ transplantation HangzhouZhejiangP.R.China Key Laboratory of the Diagnosis and Treatment of Organ transplantation Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic CancerChinese Academy of Medical SciencesHangzhouZhejiangP.R.China Key Laboratory of Organ transplantation Research Center for Diagnosis and Treatment of Hepatobiliary DiseasesHangzhouZhejiangP.R.China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP.R.China

Background:liver cancer is a malignancy with high morbidity and mortality *** family E member 2(SERPINE2)has been reported to play a key role in the metastasis of many *** this study,we aimed to investigate the potential mechanism of SERPINE2 in liver cancer ***:The Cancer Genome Atlas database(TCGA),including DNA methy-lation and transcriptome sequencing data,was utilized to identify the crucial oncogene associated with DNA methylation and cancer progression in liver *** from the TCGA and RNA sequencing for 94 pairs of liver cancer tissues were used to explore the correlation between SERPINE2 expression and clin-ical parameters of *** methylation sequencing was used to detect the DNA methylation levels in liver cancer tissues and *** sequencing,cytokine assays,immunoprecipitation(IP)and mass spectrometry(MS)assays,protein stability assays,and ubiquitination assays were performed to explore the regulatory mechanism of SERPINE2 in liver cancer ***-derived xenografts and tumor organoid models were established to determine the role of SERPINE2 in the treatment of liver cancer using ***:Based on the public database screening,SERPINE2 was identified as a tumor promoter regulated by DNA ***2 expression was significantly higher in liver cancer tissues and was associated with the dismal prognosis in patients with liver ***2 promoted liver cancer metas-tasis by enhancing cell pseudopodia formation,cell adhesion,cancer-associated fibroblast activation,extracellular matrix remodeling,and ***/MS assays confirmed that SERPINE2 activated epidermal growth factor receptor(EGFR)and its downstream signaling pathways by interacting with ***,SERPINE2 inhibited EGFR ubiquitination and maintained its protein stability by competing with the E3 ubiquitin ligase,***,EGFR was activated in liver cancer cells after sorafenib treatment,and SER

关键词： liver cancer metastasis DNA methylation SERPINE2 EGFR c-Cbl ubiquitination

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Update on the Diagnosis and Treatment of Combined Hepatocellular Cholangiocarcinoma

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Journal of Clinical and Translational Hepatology 2024年第2期12卷 210-217页

作者： Kai-Jian Chu Yoshikuni Kawaguchi Han Wang Xiao-Qing Jiang Kiyoshi Hasegawa Biliary Surgical department No.1 Eastern Hepatobiliary Surgical HospitalThe Naval Medical UniversityShanghaiChina Hepato-Biliary-pancreatic surgery Division Department of SurgeryGraduate School of MedicineThe University of TokyoTokyoJapan department of Pathology Eastern Hepatobiliary Surgical HospitalThe Naval Medical UniversityShanghaiChina

Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a unique type of liver tumor that contains both hepatocellular carcinoma and cholangiocarcinoma components within a single *** fifth edition of the World Health Organization classification provides a definition and diagnostic criteria for ***,the heterogeneous histomorphology and presentation resulting from variation of the proportion of each component poses challenges for clinical diagnosis and treatment.A diagnosis of cHCC-CCA may be suggested by the synchronous elevation of serum tumor markers for hepatocellular carcinoma and cholangiocarcinoma,a mixed enhancement pattern on imaging,and a discrepancy between the elevation of tumor marker and the imaging enhancement *** examination using hematoxylin and eosin staining is considered the gold standard for diagnosing cHCC-CCA,and comprehensive examination of resection or biopsy specimens is crucial for an accurate ***,there is no standard treatment for cHCC-CCA,and surgery is the *** hepatectomy with lymphadenectomy is among the recommended surgical *** role of liver transplantation in the management of cHCC-CCA is still *** chemoembolization may be effective for unresectable cHCC-CCA,particularly for hypervascular ***,the available evidence does not support systemic therapy for advanced *** prognosis of cHCC-CCA is generally poor,and there is no established staging *** research is needed to better understand the histogenesis and clinical management of *** review provides an overview of the current literature on cHCC-CCA with a focus on its clinical characteristics,pathological diagnosis,and management.

关键词： Combined hepatocellular-cholangiocarcinoma Clinical characteristics Imaging characteristics Pathological diagnosis Treatment

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HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

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hepatobiliary & pancreatic Diseases International 2024年第4期23卷 344-352页

作者： Qing-Zhi Hu Zhen-Rui Cao Wei-Xiong Zheng Min-Jie Zhao Jun-Hua Gong Cong Chen Zhong-Jun Wu Rui Tao department of hepatobiliary surgery Bishan Hospital of Chongqing Medical UniversityChongqing 402760China department of Cardiothoracic surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China c department of hepatobiliary surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of hepatobiliary surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune *** shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein ***:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using ***-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following *** blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular ***:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(Pliver enzymes and inflammatory chemokines in rat serum were significantly reduced(Pliver and downregulated the NF-κB pathway in the liver(Pliver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer *** HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

关键词： Ischemia-reperfusion injury liver transplantation Inflammation HSP110 Heat shock proteins NF-κB

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The differential benefit of laparoscopic over open minor liver resection for lesions situated in the anterolateral or posterosuperior segments

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hepatobiliary surgery and Nutrition 2024年第4期13卷 604-615,I0015-I0021页

作者： Jasper P.Sijberden Guido Fiorentini Jacopo Lanari Davit Aghayan Daniel Osei-Bordom Nadia Russolillo Arjun Takhar Andrea Benedetti Cacciaguerra Santi Lopez-Ben Mathieu D’Hondt Felice Giuliante David Fuks Fernando Rotellar Andrea Ruzzenente Adnan Alseidi Mikhail Efanov Burak Görgec Giuseppe Zimmitti Enrico Gringeri Federica Cipriani Åsmund Avdem Fretland Ravi Marudanayagam Marco Vivarelli John N.Primrose Alessandro Ferrero Robert P.Sutcliffe Bjørn Edwin Umberto Cillo Marc G.Besselink Mohammad Abu Hilal Luca A.Aldrighetti department of surgery Fondazione Poliambulanza Istituto OspedalieroBresciaItaly Amsterdam UMC location University of Amsterdam Department of SurgeryAmsterdamthe Netherlands Cancer Center Amsterdam Amsterdamthe Netherlands hepatobiliary surgery Division IRCCS San Raffaele HospitalMilanItaly department of Surgical Oncological and Gastroenterological SciencesGeneral Surgery 2Hepatobiliary Surgery and Liver TransplantationPadua University HospitalPaduaItaly The Intervention Centre and department of HPB surgery Oslo University Hospital and Institute of Clinical MedicineUniversity of OsloOsloNorway department of surgery Ringerike HospitalVestre Viken Hospital TrustDrammenNorway liver Unit Queen Elizabeth HospitalBirminghamUK department of General and Oncological surgery Umberto I Mauriziano HospitalLargo TuratiTurinItaly department of surgery University Hospital Southampton NHS Foundation TrustSouthamptonUK hepatobiliary and Abdominal transplantation surgery Department of Experimental and Clinical MedicineRiuniti HospitalPolytechnic University of MarcheAnconaItaly Servei de Cirurgia General i Digestiva Hospital Doctor Josep Trueta de GironaGironaCataloniaSpain department of Digestive and hepatobiliary/pancreatic surgery Groeninge HospitalKortrijkBelgium Chirurgia Epatobiliare UniversitàCattolica del Sacro Cuore-IRCCSRomeItaly department of Digestive Oncologic and Metabolic SurgeryInstitut Mutualiste MontsourisUniversitéParis DescartesParisFrance HPB and liver transplantation Unit Department of SurgeryUniversity ClinicUniversidad de NavarraNavarraSpain Institute of Health Research of Navarra(IdisNA) PamplonaSpain department of surgery University of VeronaVeronaItaly department of surgery Virginia Mason Medical CenterSeattleWAUSA department of surgery University of California San FranciscoSan FranciscoCAUSA department of Hepato-Pancreato-Biliary surgery Moscow Clinical Research CentreMoscowRussia

Background:It is well known that laparoscopic liver surgery can offer advantages over open liver surgery in selected ***,what type of procedures can benefit most from a laparoscopic approach has been investigated poorly thus *** aim of this study is thus to define the extent of advantages of laparoscopic over open liver surgery for lesions in the anterolateral(AL)and posterosuperior(PS)***:In this international multicentre retrospective cohort study,laparoscopic and open minor liver resections for lesions in the AL and PS segments were compared after propensity score *** differential benefit of laparoscopy over open liver surgery,calculated using bootstrap sampling,was compared between AL and PS resections and expressed as a Delta of the ***:After matching,3,040 AL and 2,336 PS resections were compared,encompassing open and laparoscopic procedures in a 1:1 *** and PS laparoscopic liver resections were more advantageous in comparison to open in terms of blood loss,transfusion rate,complications,and length of ***,AL resections benefitted more from laparoscopy than PS in terms of overall and severe complications(D-difference were 4.8%,P=0.046 and 3%,P=0.046)and blood loss(D-difference was 195 mL,Pliver surgery is greater in the AL segments than in the PS segments.

关键词： liver neoplasms hepatectomy laparoscopic liver resection open liver resection

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Comprehensive review of hepatocellular carcinoma with portal vein tumor thrombus:State of art and future perspectives

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hepatobiliary & pancreatic Diseases International 2024年第3期23卷 221-227页

作者： Paschalis Gavriilidis Timothy M Pawlik Daniel Azoulay department of surgery Colchester General HospitalTurner RoadColchester CO45JLUK department of surgery The Ohio State Wexner Medical CenterJames Comprehensive Cancer CenterColumbusOHUSA department of Hepato-Biliary and liver transplantation surgery Paul Brousse University HospitalParis-Saclay UniversityVillejuif 94800France

Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage *** vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if *** sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic ***:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic *** elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical *** review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of ***:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.

关键词： Hepatectomy liver surgery liver neoplasms Portal vein tumor thrombus

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FGF21-mediated autophagy:Remodeling the homeostasis in response to stress in liver diseases

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Genes & Diseases 2024年第3期11卷 264-274页

作者： Wei Shen Modan Yang Hao Chen Chiy He Huigang Li Xinyu Yang Jianyong Zhuo Zuyuan Lin Zhihang Hu Di Lu Xiao Xu Zhejiang University School of Medicine HangzhouZhejiang 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China The Institute for Organ Repair and Regenerative Medicine of Hangzhou HangzhouZhejiang 310006China Institute of Organ transplantation Zhejiang UniversityHangzhouZhejiang 310003China National Center for Healthcare Quality Management in liver Transplant HangzhouZhejiang 310003China

liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum *** exact interplay between stress and liver diseases remains *** plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver *** the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain *** recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much ***21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to ***,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal *** review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.

关键词： Autophagy Fibroblast growth factor 21 liver diseases mTOR Stress

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Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

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hepatobiliary & pancreatic Diseases International 2024年第5期23卷 463-471页

作者： Yu Nie Jin-Bo Huang Shu-Jiao He Hua-Di Chen Jun-Jun Jia Jing-Jing Li Xiao-Shun He Qiang Zhao General surgery Center Department of Hepatobiliary Surgery IIResearch Center for Artificial Organ and Tissue EngineeringGuangzhou Clinical Research and Transformation Center for Artificial LiverInstitute of Regenerative MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510515China Organ Transplant Center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology Guangzhou 510080China Guangdong Provincial International Cooperation Base of Science and Technology Guangzhou 510080China Division of hepatobiliary pancreatic surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use

关键词： Primary non-function Early allograft failure Risk predicting model liver transplantation

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To drain or not to drain after distal pancreatectomy: reflexions on the PANDORINA trial

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hepatobiliary surgery and Nutrition 2024年第4期13卷 675-677页

作者： Maxime Constant Alexandre Doussot department of Digestive and Surgical Oncology Liver Transplantation UnitCHU BesanconBesançonFrance

We read with great interest the PANDORINA study(1).This international multicenter(mostly from the Netherlands)randomized controlled trial aimed at determining whether omitting drainage after distal pancreatectomy(DP)was equivalent in terms of complications to systematic drainage *** primary outcome was the occurrence of severe complications at 90 days defined as Dindo-Clavien grade≥*** main secondary outcome was the occurrence of grade B–C postoperative pancreatic fistula(POPF)at 90 *** both outcomes,the non-inferiority threshold was set at 8%.Randomization was performed intraoperatively,stratified by annual center volume(high volume defined as DP≥40/year)and the risk of POPF according to the distal fistula risk score(D-FRS)combining pancreas thickness(high risk,>19 mm)and main pancreatic duct diameter(high risk,>3 mm)measured both at the isthmus(2).

关键词： Drainage distal pancreatectomy(DP) randomized controlled trial

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liver transplantation as an alternative for the treatment of neuroendocrine liver metastasis: Appraisal of the current evidence

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hepatobiliary & pancreatic Diseases International 2024年第2期23卷 146-153页

作者： Philip C.Muller Matthias Pfister Dilmurodjon Eshmuminov Kuno Lehmann department of surgery and transplantation University Hospital ZurichRämistrasse 100Zurich CH-8091Switzerland

Background:liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in *** comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is *** goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of *** sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March ***:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed *** liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free *** highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are *** factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic *** on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to *** benefits of LT were lost in patients beyond the Milan ***:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to *** evidence suggests even stricter selection criteria with regard to tumor biology.

关键词： liver transplantation Neuroendocrine liver metastases liver resection Selection criteria Tumor biology

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Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis

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The Innovation 2024年第3期5卷 55-68页

作者： Rui Wang Xiao Peng Yixin Yuan Baojie Shi Yuan Liu Hengxiao Ni Wenzhi Guo Qiwei Yang Pingguo Liu Jie Wang Zhaojie Su Shengnan Yu Dehua Liu Jinyan Zhang Junjie Xia Xueni Liu Hao Li Zhengfeng Yang Zhihai Peng Organ transplantation Clinical Medical Center of Xiamen University Department of General SurgeryXiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China Organ transplantation Institute of Xiamen University Xiamen Human Organ Transplantation Quality Control CenterXiamen Key Laboratory of Regeneration MedicineFujian Provincial Key Laboratory of Organ and Tissue RegenerationSchool of MedicineXiamen UniversityXiamen 361102China department of General surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China department of hepatobiliary and pancreatic surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China department of hepatobiliary&pancreatic surgery The National Key Clinical SpecialtyZhongshan Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China Precision Research Center for Refractory Diseases Institute for Clinical ResearchShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201620China

Elucidating the temporal process of immune remodeling under immunosuppressive treatment after liver transplantation(LT)is critical for precise clinical management ***,we performed a single-cell multi-omics analysis of peripheral blood mononuclear cells(PBMCs)collected from LT patients(with and without acute cellular rejection[ACR])at 13 time *** was performed in two independent cohorts with additional LT patients and healthy *** study revealed a four-phase recovery process after LT and delineated changes in immune cell composition,expression programs,and interactions along this *** intensity of the immune response differs between the ACR and non-ACR ***,the newly identified inflamed NK cells,CD14+RNASE2+monocytes,and FOS-expressing monocytes emerged as predictive indicators of *** study illuminates the longitudinal evolution of the immune cell landscape under tacrolimus-based immunosuppressive treatment during LT recovery,providing a four-phase framework that aids the clinical management of LT patients.

关键词： process analysis precise

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