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In silico analysis of lncRNA-miRNA-mRNA signatures related to Sorafenib effectiveness in liver cancer cells

World Journal of Gastroenterology 2025年第3期31卷 84-102页

作者： Patricia de la Cruz-Ojeda Ester Parras-Martínez Raquel Rey-Pérez Jordi Muntané Functional Genomics of Solid Tumors Laboratory Centre de Recherche des CordeliersParis 75006France Department of Oncology Surgery Cell Therapy and Organ TransplantationInstitute of Biomedicine of SevilleVirgen del Rocio University HospitalSeville 41013Spain Biomedical Research Center for Hepatic and Digestive Diseases CIBERehdMadrid 28029Spain Department of Medical Physiology and Biophysics University of SevilleSeville 41009Spain

BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology *** is still a recommended treatment for a large proportion of patients with advanced *** patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 *** To define the long non-codingRNA-microRNA-mRNA(lncRNA-miRNA-mRNA)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in RNAseq studies using Sorafenib-treated HepG2 and SNU449 *** available software analyses allowed us to establish the lncRNA-miRNA-mRNA regulatory axes following treatment in HepG2 and SNU449 *** HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 *** RNA,including small and long RNA,was extracted with a commercial miRNeasy *** was carried out for the identification of changes in lncRNA-miRNA-mRNA regulatory *** MALAT,THAP9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7,TIRARP,TFAP4 and FAXDC2 in HepG2 ***12,EPB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,miR-195-5p and VEGFA in SNU449 *** axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAP4 were of high relevance for Sorafenib response in HepG2 cells,whereas PVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib *** Critical lncRNAs acting as sponges of miRNA were identified that regulated mRNA expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIRARP,TFAP4,FAXDC2 and ADRB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.

关键词： Cell culture Hepatocellular carcinoma Non-coding RNA RNAseq Sorafenib

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Global transplantation:Lessons from organ transplantation organizations worldwide

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World Journal of transplantation 2025年第1期15卷 44-56页

作者： Solonas Symeou Eleni Avramidou Vassilios Papalois Georgios Tsoulfas Medical School University of IoanninaIoannina 45110Greece Department of transplantation Surgery Center for Research and Innovation in Solid Organ TransplantationSchool of MedicineAristotle University of ThessalonikiThessaloniki 54642Greece Imperial College Renal and Transplant centre Imperial College Healthcare NHS TrustHammersmith HospitalLondon W120HSUnited Kingdom Department of Surgery and Cancer Imperial College LondonLondon SW72AZUnited Kingdom

Although national transplant organizations share common visions and goals,the creation of a unified global organization remains *** in ethnicity,culture,religion,and education shape local practices and infrastructure,making the establishment of a single global entity *** with these social disparities aside,logistical factors such as time and distance between organ procurement and transplantation sites pose significant *** technological advancements have extended organ preservation times,they have yet to support the demands of transcontinental transplantations *** review presents a comparative analysis of the structures,operational frameworks,policies,and legislation governing various transplant organizations around the *** differences pertain to the administration of these organizations,trends in organ donation,and organ allocation policies,which reflect the financial,cultural,and religious diversity across different *** a global transplant organization may be out of reach,agreeing on best practices for the benefit of patients is essential.

关键词： Organ transplantation National transplant organizations Organ donation Global transplantation Transplant systems

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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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Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation

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World Journal of Clinical Cases 2019年第3期7卷 270-290页

作者： Evaldo Favi Carmelo Puliatti Rajesh Sivaprakasam Mariano Ferraresso Federico Ambrogi Serena Delbue Federico Gervasi Ilaria Salzillo Nicholas Raison Roberto Cacciola Renal transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico Renal transplantation Barts Health NHS Trust Royal London Hospital Department of Clinical Sciences and Community Health University of Milan Department of Biomedical Surgical and Dental Sciences University of Milan mrc centre for transplantation King’s College London

BACKGROUND Polyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless,long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also *** To investigate incidence, risk factors, and outcome of BK-virus infection after kidney *** This single-centre observational study with a median follow up of 57(31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasmaquantitative polymerized chain reaction. Patients with BK viral load ≥ 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment,rejection, renal function, urologic complications, opportunistic infections, newonset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and *** BK-viremia was detected in 9.5% recipients. Initial viral load was high(≥ 10000 copies/mL) in 66.7% and low(< 10000 copies/mL) in 33.3% of these ***-associated nephropathy was diagnosed in 6.5% of the study population. Patients with high initial viral load were more likely to experience sustained viremia(95% vs 25%, P < 0.00001), nephropathy(92.

关键词： Polyomavirus BK virus Kidney transplantation Outcome Risk factors Immunosuppression Human leukocyte antigen Rejection Cytomegalovirus Ethnicity

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Malaria after living donor liver transplantation:report of two cases

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Hepatobiliary & Pancreatic Diseases International 2008年第2期7卷 210-213页

作者： Durgatosh Pandey Kan-Hoe Lee Sin-Yew Wong Kai-Chah Tan Department of Hepatobiliary Surgery and Liver transplantation Asian centre for Liver Diseases and transplantation Gleneagles Hospital Singapore Department of Respiratory Medicine and Intensive Care Asian centre for Liver Diseases and transplantation Gleneagles Hospital Singapore Department of Infectious Diseases Asian centre for Liver Diseases and transplantation Gleneagles Hospital Singapore

BACKGROUND:Infectious complications are common during the postoperative course of a liver transplant recipient. Malaria, however, is a rare complication in such a setting. METHOD:We report post-transplantation malaria causing elevation of liver enzymes in two recipients. RESULTS:Both patients who had undergone living donor liver transplantation showed elevated levels of liver enzymes and fever during the postoperative course. Investigations (including liver biopsy in one patient) were initially inconclusive in determining the cause of liver dysfunction. The diagnosis of malaria was established in both cases by peripheral blood smear. Liver function transiently worsened with antimalarial treatment but subsequently became normal. CONCLUSION:This report highlights the importance of excluding such uncommon causes of post-transplantation liver dysfunction, especially when either the recipient or the donor comes from a region endemic for malaria.

关键词： liver transplantation malaria recipient

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Biomarkers in Barrett's esophagus and esophageal adenocarcinoma:Predictors of progression and prognosis

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World Journal of Gastroenterology 2010年第45期16卷 5669-5681页

作者： Chin-Ann J Ong Pierre Lao-Sirieix Rebecca C Fitzgerald mrc Cancer Cell Unit Hutchison-MRC Research CentreCambridgeCB20XZUnited Kingdom

Barrett’s esophagus is a well-known premalignant lesion of the lower esophagus that is characterized by intestinal metaplasia of the squamous epithelium. It is clinically important due to the increased risk (0.5% per annum) of progression to esophageal adenocarcinoma (EA), which has a poor outcome unless diagnosed early. The current clinical management of Barrett’s esophagus is hampered by the lack of accurate predictors of progression. In addition, when patients develop EA, the current staging modalities are limited in stratifying patients into different prognostic groups in order to guide the optimal therapy for an individual patient. Biomarkers have the potential to improve radically the clinical management of patients with Barrett’s esophagus and EA but have not yet entered mainstream clinical practice. This is in contrast to other cancers like breast and prostate for which biomarkers are utilized routinely to inform clinical decisions. This review aims to highlight the most promising predictive and prognostic biomarkers in Barrett’s esophagus and EA and to discuss what is required to move the field forward towards clinical application.

关键词： Barrett’s esophagus Esophageal adenocar cinoma Esophageal dysplasia Prognosis

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Synchronous splenectomy and hepatectomy for patients with hepatocellular carcinoma and hypersplenism:A casecontrol study

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World Journal of Gastroenterology 2015年第8期21卷 2358-2366页

作者： Xiao-Yun Zhang Chuan Li Tian-Fu Wen Lu-Nan Yan Bo Li Jia-Yin Yang Wen-Tao Wang Li Jiang Department of Liver Surgery and Liver transplantation centre West China Hospital of Sichuan University

AIM:To investigate whether the use of synchronoushepatectomy and splenectomy(HS)is more effective than hepatectomy alone(HA)for patients with hepatocellular carcinoma(HCC)and ***:From January 2007 to March 2013,84consecutive patients with HCC and hypersplenism who underwent synchronous hepatectomy and splenectomy in our center were compared with 84 well-matched patients from a pool of 268 patients who underwent hepatectomy *** short-term and longterm outcomes of the two groups were analyzed and ***:The mean time to recurrence was 21.11±12.04 mo in the HS group and 11.23±8.73 mo in the HA group,and these values were significantly different(P=0.001).The 1-,3-,5-,and 7-year disease-free survival rates for the patients in the HS group and the HA group were 86.7%,70.9%,52.7%,and 45.9%and 88.1%,59.4%,43.3%,and 39.5%,respectively(P=0.008).Platelet and white blood cell counts in the HS group were significantly increased compared with the HA group one day,one week,one month and one year postoperatively(P<0.001).Splenectomy and micro-vascular invasion were significant independent prognostic factors for disease-free ***,tumor number,and recurrence were independent prognostic factors for overall ***:Synchronous hepatectomy and hepatectomy potentially improves disease-free survival rates and alleviates hypersplenism without increasing the surgical risks for patients with HCC and hypersplenism.

关键词： Hepatocellular carcinoma Hypersplenism Splenectomy

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Extracellular vesicles as mediators of alloimmunity and their therapeutic potential in liver transplantation

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World Journal of transplantation 2020年第11期10卷 330-344页

作者： Sotiris Mastoridis Marc Martinez-Llordella Alberto Sanchez-Fueyo Department ofSurgery Oxford University HospitalsOxford OX37LEUnited Kingdom Institute of Liver Studies King's College HospitalMedical Research Council(MRC)Centre for TransplantationLondon SE59NUUnited Kingdom Department of Liver Sciences King's College HospitalMedical Research Council(MRC)Centre for TransplantationLondon SE59NUUnited Kingdom

Extracellular vesicles(EVs)are a heterogenous group of nanosized,membranebound particles which are released by most cell *** are known to play an essential role in cellular communication by way of their varied cargo which includes selectively enriched proteins,lipids,and nucleic *** the last two decades,wide-ranging evidence has established the involvement of EVs in the regulation of immunity,with EVs released by immune and non-immune cells shown to be capable of mediating immune stimulation or suppression and to drive inflammatory,autoimmune,and infectious disease *** recently,studies have demonstrated the involvement of allograft-derived EVs in alloimmune responses following transplantation,with EVs shown to be capable of eliciting allograft rejection as well as promoting *** insights are necessitating the reassessment of standard paradigms of T cell *** this article,we explore the latest understanding of the impact of EVs on alloresponses following transplantation and we highlight the recent technological advances which have enabled the study of EVs in clinical ***,we discuss the rapid progress afoot in the development of EVs as novel therapeutic vehicles in clinical transplantation with particular focus on liver transplantation.

关键词： Extracellular vesicle transplantation Liver Alloimmunity Tolerance Therapy

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Immunosuppression in Human Peripheral Blood T Lymphocytes by Fluvastatin

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Acta Biochimica et Biophysica Sinica 2004年第10期36卷 649-655页

作者： Li-Hua WU, Yun-Le WAN1, Hai-Yang XIE, Wen-Jin ZHANG, and Shu-Sen ZHENG* Institute of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China 1centre of organ transplantation, The Second Affiliated Hospital, School of Medicine, Zhongshan University, Guangzhou 510000, China Institute of Surgery The First Affiliated Hospital School of Medicine Zhejiang University centre of organ transplantation The Second Affiliated Hospital School of Medicine Zhongshan University

To investigate the immunosuppressive effect of fluvastatin on the PHA-activated T lymphocytes. T lymphocytes were isolated from the blood of healthy volunteers, cell proliferation and the activation mar- kers expression were examined by flow cytometric analysis. Cytokine secretion was assayed by ELISA. LDH-release assay was used to detect activity of killer cells. NFAT activation was evaluated by TransAMTM ELISA kit. Results were as following. (1) Whereas no modification in CD25 expression was seen, fluvastatin at 5 μM caused a lower level of CD69 expression, accompanied by an essential suppression on proliferation, IL-2 production and cytotoxicity development in PHA-stimulated T cells. However, the level of secreted IL-10 had no change, and the level of IL-4 even experienced a significant increase. (2) Combined with cyclosporine A (CsA), fluvastatin would further repress CD69 expression, cells proliferation and activity of killer cells, meanwhile significantly induced the secretion of IL-4 and IL-10. (3) Fluvastatin treatment also resulted in a strong inhibition of NFAT activation. In conclusion, partly involving the blockage of activation of NFAT, fluvastatin exhibited an immunosuppressive effect in vitro.

关键词： fluvastatin T cell activation T cell proliferation cytokine nuclear factor of activated Tlymphocytes

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Breath Biopsy^(®) to Identify Exhaled Volatile Organic Compounds Biomarkers for Liver Cirrhosis Detection

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 638-648页

作者： Giuseppe Ferrandino Giovanna De Palo Antonio Murgia Owen Birch Ahmed Tawfike Rob Smith Irene Debiram-Beecham Olga Gandelman Graham Kibble Anne Marie Lydon Alice Groves Agnieszka Smolinska Max Allsworth Billy Boyle Marc P.van der Schee Michael Allison Rebecca C.Fitzgerald Matthew Hoare Victoria K.Snowdon Owlstone Medical CambridgeUK Department of Oncology University of CambridgeHutchison/MRC Research CentreCambridgeUK Department of Pharmacology and Toxicology School for Nutrition and Translational Research in Metabo-lism(NUTRIM)Maastricht University Medical Centerthe Netherlands Department of Medicine University of CambridgeAddenbrooke’s HospitalCambridgeUK Addenbrookes Hepatology and Liver transplantation Unit Addenbrookes Hospi-talCambridgeUK mrc Cancer Unit Hutchison/MRC Research CentreUniversity of CambridgeCambridgeUK CRUK Cambridge Institute CambridgeUK

Background and Aims:The prevalence of chronic liver dis-ease in adults exceeds 30%in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce healthcare *** is a rich sampling matrix that offers non-invasive so-lutions suitable for early-stage detection and disease *** previously investigated targeted analysis of a single biomarker,here we investigated a multiparametric approach to breath testing that would provide more robust and reliable results for clinical ***:To identify can-didate biomarkers we compared 46 breath samples from cir-rhosis patients and 42 from *** and analysis used Breath Biopsy OMNI™,maximizing signal and contrast to background to provide high confidence biomarker detec-tion based upon gas chromatography mass spectrometry(GC-MS).Blank samples were also analyzed to provide de-tailed information on background volatile organic compounds(VOCs)***:A set of 29 breath VOCs differed significantly between cirrhosis and controls.A classification model based on these VOCs had an area under the curve(AUC)of 0.95±0.04 in cross-validated test *** seven best performing VOCs were sufficient to maximize classifica-tion performance.A subset of 11 VOCs was correlated with blood metrics of liver function(bilirubin,albumin,prothrom-bin time)and separated patients by cirrhosis severity using principal component ***:A set of seven VOCs consisting of previously reported and novel candidates show promise as a panel for liver disease detection and mon-itoring,showing correlation to disease severity and serum biomarkers at late stage.

关键词： Breath Biopsy Non-invasive Biomarker Cirrhosis Liver function test.

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