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Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

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World Journal of Gastroenterology 2025年第1期31卷 126-145页

作者： Xing-Hui Yu Yan Xie Jian Yu Kun-Ning Zhang Zhou-Bo Guo Di Wang Zhao-Xian Li Wei-Qi Zhang Yu-Ying Tan Li Zhang Wen-Tao Jiang School of Medicine Nankai UniversityTianjin 300192China Tianjin Key Laboratory of Molecular Diagnosis and Treatment of liver Cancer Tianjin First Center HospitalTianjin 300192China Department of liver transplantation Tianjin First Center HospitalTianjin 300192China First Central Clinical School Tianjin Medical UniversityTianjin 300192China

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated *** therapeutic targets are beneficial to treat and predict the ***,the exact molecular mechanisms leading to the progression of HCC are still *** has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor *** this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between *** To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC *** In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC ***,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,*** statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank *** In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival ***1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated ***,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via *** the exploration mechanism,we found ASH1L may promote an immunosuppressive mi

关键词： Hepatocellular carcinoma MicroRNA-142-3p ASH1L Immune evasion Tumor immune microenvironment Apoptosis

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Pretreatment red blood cell distribution width as a predictive marker for postoperative complications after laparoscopic pancreatoduodenectomy

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 143-157页

作者： Xian-Rang Cao Yin-Long Xu Jia-Wei Chai Kai Zheng Jun-Jie Kong Jun Liu Shun-Zhen Zheng Department of liver transplantation and Hepatobiliary Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina Department of Breast and Thyroid Surgery Shandong Provincial Maternal and Child Health Care HospitalJinan 250014Shandong ProvinceChina

BACKGROUND Red blood cell distribution width(RDW)is associated with the development and progression of various *** To explore the association between pretreatment RDW and short-term outcomes after laparoscopic pancreatoduodenectomy(LPD).METHODS A total of 804 consecutive patients who underwent LPD at our hospital between March 2017 and November 2021 were retrospectively *** between pretreatment RDW and clinicopathological characteristics and short-term outcomes were *** Patients with higher pretreatment RDW were older,had higher Eastern Cooperative Oncology Group scores and were associated with poorer short-term outcomes than those with normal *** pretreatment RDW was an independent risk factor for postoperative complications(POCs)(hazard ratio=2.973,95%confidence interval:2.032-4.350,P<0.001)and severe POCs of grade IIIa or higher(hazard ratio=3.138,95%confidence interval:2.042-4.824,P<0.001)based on the Clavien-Dino classification *** analysis showed that high pretreatment RDW was an independent risk factor for Clavien-Dino classi-fication grade IIIb or higher POCs,a comprehensive complication index score≥26.2,severe postoperative pancreatic fistula,severe bile leakage and severe *** pretreatment RDW was positively associated with the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and was negatively associated with albumin and the prognostic nutritional *** Pretreatment RDW was a special parameter for patients who underwent *** was associated with malnutrition,severe inflammatory status and poorer short-term *** could be a surrogate marker for nutritional and inflammatory status in identifying patients who were at high risk of developing POCs after LPD.

关键词： Biomarker Laparoscopic pancreatoduodenectomy Postoperative complication Red blood cell distribution width Short-term outcomes

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Haemoxygenase modulates cytokine induced neutrophil chemoattractant in hepatic ischemia reperfusion injury

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World Journal of Gastroenterology 2016年第33期22卷 7518-7535页

作者： Niteen Tapuria Sameer Junnarkar Mahmoud Abu-amara Barry Fuller Alexander M Seifalian Brian R Davidson Department of hpb Surgery and liver transplantation Royal Free Hospital

AIM To investigate the hepatic microcirculatory changes due to Haemoxygenase(HO),effect of HO inhibition on remote ischemic preconditioning(RIPC) and modulation of *** Eight groups of animals were studied- Sham,ischemia reperfusion injury(IRI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion,RIPC(remote ischemic preconditioning) + IRI group,remote ischemic preconditioning in sham(RIPC + Sham),PDTC + IR(Pyridodithiocarbamate,HO donor),Zn PP + RIPC + IRI(Zinc protoporphyrin prior to preconditioning),IR-24(45 min of ischemia followed by 24 h of reperfusion),RIPC+IR-24(preconditioning prior to. After 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were taken. RESULTS Velocity of flow(160.83 ± 12.24 μm/s),sinusoidal flow(8.42 ± 1.19) and sinusoidal perfusion index(42.12 ± 7.28) in hepatic IR were lower(P < 0.05) in comparison to RIPC and PDTC(HO inducer). RIPC increased velocity of flow(328.04 ± 19.13 μm/s),sinusoidal flow(17.75 ± 2.59) and the sinusoidal perfusion index(67.28 ± 1.82)(P < 0.05). PDTC(HO induction) reproduced the effects of RIPC in hepatic IR. PDTC restored RBC velocity(300.88 ± 22.109 μm/s),sinusoidal flow(17.66 ± 3.71) and sinusoidal perfusion(82.33 ± 3.5) to near sham levels. Zn PP(HO inhibition) reduced velocity of flow of RBC in the RIPC group(170.74 ± 13.43 μm/s and sinusoidal flow in the RIPC group(9.46 ± 1.34). Zn PP in RIPC(60.29 ± 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in IR injury is seen in both postsinusoidal venules(769.05 ± 87.48) and sinusoids(97.4 ± 7.49). Neutrophil adhesion in RIPC + IR injury is reduced in both postsinusoidal venules(219.66 ± 93.79) and sinusoids(25.69 ± 9.08)(P < 0.05). PDTC reduced neutrophil adhesion in both postsinusoidal venules(89.58 ± 58.32) and sinusoids(17.98 ± 11.01)(P < 0.05) reproducing the effects of RIPC. Zn PP(HO inhibition) increased venular(589.04 ± 144.36) and sinusoida

关键词： Reperfusion injury CINC Microcirculation Ischaemic preconditioning Remote preconditioning Haemoxygenase

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Role of colectomy in preventing recurrent primary sclerosing cholangitis in liver transplant recipients

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World Journal of Gastroenterology 2018年第28期24卷 3171-3180页

作者： Bettina M Buchholz Panagis M Lykoudis Reena Ravikumar Joerg M Pollok Giuseppe K Fusai Department of hpb Surgery and liver transplantation Royal Free Hospital London

AIM To study the published evidence on the impact of colectomy in preventing recurrent primary sclerosing cholangitis(r PSC). METHODS An unrestricted systematic literature search in Pub Med, EMBASE, Medline Ovid SP, ISI Web of Science, Lista(EBSCO) and the Cochrane library was performed on clinical studies investigating colectomy in liver transplantation(LT) recipients with and without r PSC in the liver allograft. Study quality was evaluated according to a modification of the methodological index for non-randomized studies(MINORS) criteria. Primary endpoints were the impact of presence, timing and type of colectomy on r PSC. Overall presence of inflammatory bowel disease(IBD), time of IBD diagnosis, posttransplant IBD and immunosuppressive regimen were investigated as secondary *** The literature search yielded a total of 180 publications. No randomized controlled trial was identified. Six retrospective studies met the inclusion criteria of which 5 studies were graded as high quality articles. Reporting of IBD was heterogenous but in four publications, either inflammatory bowel disease, ulcerative colitis or in particular active colitis post-LT significantly increased the risk of r PSC. The presence of an intact(i.e., retained) colon at LT was identified as risk factor for r PSC in two of the high quality studies while four studies found no effect. Type of colectomy was not associated with r PSC but this endpoint was underreported(only in 33% of included studies).Neither tacrolimus nor cyclosporine A yielded a significant benefit in disease recurrence of primary sclerosing cholangitis(PSC).CONCLUSION The data favours a protective role of pre-/peri-LT colectomy in r PSC but the current evidence is not strong enough to recommend routine colectomy for r PSC prevention.

关键词： Recurrent primary sclerosing cholangitis Risk factor Ulcerative colitis Colectomy liver transplantation

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Current protective strategies in liver surgery

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World Journal of Gastroenterology 2010年第48期16卷 6098-6103页

作者： Kurinchi S Gurusamy Hector D Gonzalez Brian R Davidson hpb and liver transplantation Royal Free CampusUniversity College London Medical SchoolRoyal Free Hospital

During liver resection surgery for cancer or liver transplantation,the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow),which results in liver injury [ischemiareperfusion (IR) or IR injury]. Modulation of IR injury can be achieved in various ways. These include hypothermia,ischaemic preconditioning (IPC) (brief cycles of ischaemia followed by reperfusion of the organ before the prolonged period of ischaemia i.e. a conditioning response),ischaemic postconditioning (conditioning after the prolonged period of ischaemia but before the reperfusion),pharmacological agents to decrease IR injury,genetic modulation of IR injury,and machine perfusion (pulsatile perfusion). Hypothermia decreases the metabolic functions and the oxygen consumption of organs. Static cold storage in University of Wisconsin solution reduces IR injury and has prolonged organ storage and improved the function of transplanted grafts. There is currently no evidence for any clinical advantage in the use of alternate solutions for static cold storage. Although experimental data from animal models suggest that IPC,ischaemic postconditioning,various pharma-cological agents,gene therapy,and machine perfusion decrease IR injury,none of these interventions can be recommended in clinical practice. This is because of the lack of randomized controlled trials assessing the safety and efficacy of ischaemic postconditioning,gene therapy,and machine perfusion. Randomized controlled trials and systematic reviews of randomized controlled trials assessing the safety and efficacy of IPC and various pharmacological agents have demonstrated biochemical or histological improvements but this has not translated to clinical benefit. Further well designed randomized controlled trials are necessary to assess the various new protective strategies in liver resection.

关键词： liver Hepatectomy liver transplantation Ischemia-reperfusion injury Hypothermia Ischaemic preconditioning

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Incidental gallbladder cancer diagnosis confers survival advantage irrespective of tumour stage and characteristics

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World Journal of Gastroenterology 2022年第18期28卷 1996-2007页

作者： Moath Alarabiyat Syed Soulat Raza John Isaac Darius Mirza Ravi Marudanayagam Keith Roberts Manuel Abradelo David C Bartlett Bobby V Dasari Robert P Sutcliffe Nikolaos A Chatzizacharias hpb and liver Transplant Unit Queen Elizabeth HospitalBirmingham B152GWUnited Kingdom Department of hpb and liver transplantation Queen Elizabeth HospitalUniversity Hospitals BirminghamBirmingham B152THUnited Kingdom

BACKGROUND Incidental gallbladder cancer(IGBC)represents 50%-60%of gallbladder cancer *** are conflicting on the role of IGBC diagnosis in oncological *** studies suggest that IGBC diagnosis does not affect outcomes,while others that overall survival(OS)is longer in these cases compared to non-incidental diagnosis(NIGBC).Furthermore,some studies reported early tumour stages and histopathologic characteristics as possible confounders,while others *** To investigate the role of IGBC diagnosis on patients’overall survival,especially after surgical treatment with curative *** Retrospective analysis of all patient referrals with gallbladder cancer between 2008 and 2020 in a tertiary hepatobiliary *** comparison of patient and tumour characteristics between IGBC and NIGBC subgroups was *** analysis for the whole cohort,surgical and non-surgical subgroups was done with the Kaplan-Meier method and the use of log rank *** analysis was performed with univariable and multivariable Cox regression *** The cohort included 261 patients with gallbladder cancer.65%of cases had NIGBC and 35%had IGBC.A total of 90 patients received surgical treatment(66%of IGBC cases and 19%of NIGBC cases).NIGBC patients had more advanced T stage and required more extensive resections than IGBC *** was longer in patients with IGBC in the whole cohort(29 vs 4 mo,P<0.001),as well as in the non-surgical(14 vs 2 mo,P<0.001)and surgical subgroups(29 vs 16.5 mo,P=0.001).Disease free survival(DFS)after surgery was longer in patients with IGBC(21.5 mo vs 8.5 mo,P=0.007).N stage and resection margin status were identified as independent predictors of OS and *** diagnosis was identified as an independent predictor of *** IGBC diagnosis may confer a survival advantage independently of the pathological stage and tumour *** studies are required to further investigate this,including detailed

关键词： Gallbladder cancer Incidental gallbladder cancer Non-incidental gallbladder cancer Gallbladder cancer survival

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A gist of gastrointestinal stromal tumors: A review

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World Journal of Gastrointestinal Oncology 2013年第6期5卷 102-112页

作者： Ashwin Rammohan Jeswanth Sathyanesan Kamalakannan Rajendran Anbalagan Pitchaimuthu Senthil-Kumar Perumal UP Srinivasan Ravi Ramasamy Ravichandran Palaniappan Manoharan Govindan The Institute of Surgical Gastroenterology and liver transplantation Centre for GI Bleed Division of HPB Diseases Stanley Medical College Hospital

Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mes-enchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularlytargeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.

关键词： Gastrointestinal stromal tumors c-KIT Imatinib mesylate Surgery Review

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Double cholecystectomy in case of accessory gallbladder:Not as easy as two cholecystectomies

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Hepatobiliary & Pancreatic Diseases International 2019年第1期18卷 93-95页

作者： Benjamin Darnis Kayvan Mohkam Fran?ois Cauchy Jean-Yves Mabrut Department of General Surgery and liver transplantation Hospices Civils de Lyon Croix-Rousse University Hospital Ecole Doctorale EDISS 205 Université Lyon 1 hpb Surgery and liver transplantation Unit Beaujon Hospital

To the Editor:Accessory gallbladders(AG)are rare and their management are usually *** variations are related with an abnormal division of the bile ducts precursors between the 5th and the 12th week of *** et al.[1]proposed an anatomical classification of these variations based on the embryologic abnormalities *** type 1 both gallbladders are connected to the common bile duct at the same *** type 2 the AG can reach either the common bile duct(ductular type)or an intrahepatic biliary duct(trabecular type).In type 3,three gallbladders are present.

关键词： gallbladders Harlaftis

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Risk factors and classifications of hilar cholangiocarcinoma

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World Journal of Gastrointestinal Oncology 2013年第7期5卷 132-138页

作者： Miguel Angel Suarez-Munoz Jose Luis Fernandez-Aguilar Belinda Sanchez-Perez Jose Antonio Perez-Daga Beatriz Garcia-Albiach Ysabel Pulido-Roa Naiara Marin-Camero Julio Santoyo-Santoyo General Digestive and transplantation Surgery Service HPB and Liver Transplant UnitUniversity Hospital Carlos Haya29010 MalagaSpain

Cholangiocarcinoma is the second most common primary malignant tumor of the *** cholangiocarcinoma or Klatskin tumor represents more than 50% of all biliary tract cholangiocarcinomas.A wide range of risk factors have been identified among patients with Perihilar cholangiocarcinoma including advanced age,male gender,primary sclerosing cholangitis,choledochal cysts,cholelithiasis,cholecystitis,parasitic infection(Opisthorchis viverrini and Clonorchis sinensis),inflammatory bowel disease,alcoholic cirrhosis,nonalcoholic cirrhosis,chronic pancreatitis and metabolic *** classifications have been used to describe the pathologic and radiologic appearance of *** three systems most commonly used to evaluate Perihilar cholangiocarcinoma are the Bismuth-Corlette(BC) system,the Memorial Sloan-Kettering Cancer Center and the TNM *** BC classification provides preoperative assessment of local *** Memorial Sloan-Kettering cancer center proposes a staging system according to three factors related to local tumor extent:the location and extent of bile duct involvement,the presence or absence of portal venous invasion,and the presence or absence of hepatic lobar *** TNM classification,besides the usual descriptors,tumor,node and metastases,provides additional information concerning the possibility for the residual tumor(R) and the histological grade(G).Recently,in 2011,a new consensus classification for the Perihilar cholangiocarcinoma had been *** consensus was organised by the European Hepato-PancreatoBiliary Association which identified the need for a new staging system for this type of *** classification includes information concerning biliary or vascular(portal or arterial) involvement,lymph node status or metastases,but also other essential aspects related to the surgical risk,such as remnant hepatic volume or the possibility of underlying disease.

关键词： Hilar cholangiocarcinoma Klatskin tumor Perihilar cholangiocarcinoma Bile duct cancer

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The role of liver transplantation for hilar cholangiocarcinoma

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Hepatobiliary & Pancreatic Diseases International 2007年第3期6卷 248-253页

作者： Durgatosh Pandey Kang-Hoe Lee Kai-Chah Tan Hepatobiliary Surgery & liver transplantation Asian Centre for Liver Disease and Transplantation Gleneagles Hospital Singapore

BACKGROUND: Hilar cholangiocarcinoma is a devastating disease. Surgery is the only potentially curative modality. However, the results of surgical resection for hilar cholangiocarcinomas are disappointing. The introduction of liver transplantation for this condition has brought new hope for the management of this disease. The aim of this review is to discuss the role of liver transplantation in this disease. DATA SOURCES: A MEDLINE search was conducted for the articles on liver transplantation for hilar cholangiocarcinoma. Their results have been compiled and compared with the existing literature on resection for this disease. RESULTS: The earlier series on liver transplantation for hilar cholangiocarcinoma were not encouraging because of poor patient selection. The Mayo Clinic protocol of neoadjuvant chemoradiation followed by liver transplantation has shown remarkable success (survival at 1-, 3-, and 5-year post-transplantation being 92%, 82%, and 82%, respectively). With better patient selection and integration of neoadjuvant chemoradiation, the long-term survival is superior to that of the patients who undergo resection, as shown by the published literature on resection. The limitations of organ availability can be overcome by the living donor liver transplantation programme. This review article discusses the rationale, pros and cons of liver transplantation vis-à-vis resection for hilar ***: liver transplantation, especially living donor liver transplantation, is a new and exciting alternative to resection for hilar cholangiocarcinoma. Integration of neoadjuvant chemoradiation has the potential to further improve the curative potential of liver transplantation. The strategy of combining neoadjuvant chemoradiation and liver transplantation brings new hope for the treatment of this difficult disease.

关键词： liver transplantation hilar cholangiocarcinoma neoadjuvant chemoradiation.

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