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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

Science China Life Sciences 2025年第1期 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal Cancer Center Peking University Cancer Hospital & Institute Department of liver Surgery & transplantation Liver Cancer InstituteZhongshan HospitalFudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Current perspectives on the role of liver transplantation for Langerhans cell histiocytosis:A narrative review

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World Journal of Gastroenterology 2022年第30期28卷 4044-4052页

作者： Jagadeesh Menon Ashwin Rammohan Mukul Vij Naresh Shanmugam Mohamed Rela institute of liver disease&transplantation Dr.Rela Institute&Medical CentreBharath Institute of Higher Education&ResearchChennai 600044India

Langerhans cell histiocytosis(LCH)is a malignant disease of the histiocytes involving various organ *** spectrum of liver involvement in LCH ranges from mild transaminitis to end-stage liver *** hallmark of hepatic LCH is secondary sclerosing cholangitis,which manifests due to a progressive destruction of the biliary tree by malignant *** remains the mainstay of treatment for active *** recognition,diagnosis and a systematic approach to the management of LCH can ameliorate the disease ***,the liver involvement in these patients may progress despite the LCH being in *** transplantation(LT)remains central in the management of such *** facets of the management of LCH,especially those with liver involvement remain ***,aspects of LT in LCH with regards to the indication,timing and post-LT management,including immunosuppression and adjuvant therapy,remain *** review summarises the current evidence and discusses the practical aspects of the role of LT in the management of LCH.

关键词： Langerhans cell histiocytosis liver transplantation Outcomes Management Chemotherapy Ethics

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Robotic donor hepatectomy:Are we there yet?

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World Journal of Gastrointestinal Surgery 2021年第7期13卷 668-677页

作者： Ashwin Rammohan Mohamed Rela institute of liver disease&transplantation Dr.Rela Institute&Medical CentreBharath Institute of Higher Education&ResearchChennai 600044India

In living donor liver transplantation(LDLT)the safety of the live donor(LD)is of paramount *** all efforts,the morbidity rates approach 25%-40%with conventional open donor hepatectomy(DH)***,most of these complications are related to the operative wound and despite increased selfesteem and satisfaction in various quality of life analyses on LD,the most common grievance is that of the *** safe and precise DH through a conventional laparoscopic approach is a formidable task with a precipitous learning curve for the whole *** to the ramifications the donor operation carries for the donor,the recipient,the transplant team and for the LDLT program in general,the development and acceptance of minimally invasive DH(MIDH)has been *** robotic surgical system overcomes the reduced visualization,restricted range of motion and physiological tremor associated with laparoscopic surgery and allows for a comparatively easier transition from technical feasibility to ***,many questions especially with regards to standardization of surgical technique,comparison of outcomes,understanding of the learning curve,*** *** aim of this review is to provide insights into the evolution of MIDH and highlight the current status of robotic DH,appreciating the existing challenges and its future role.

关键词： liver transplantation Donor hepatectomy Minimal invasive surgery Robotic surgery Outcomes

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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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Post-COVID-19 cholangiopathy:Current understanding and management options

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World Journal of Gastrointestinal Surgery 2023年第5期15卷 788-798页

作者： Fadl H Veerankutty Kushan Sengupta Mukul Vij Ashwin Rammohan Dinesh Jothimani Ananthavadivelu Murali Mohamed Rela institute of liver disease and transplantation Dr.Rela Institute and Research CentreChennai 600044India institute of liver disease and transplantation Dr.Rela Institute and Medical CentreChennai 600044India Department of Pathology Institute of Liver Disease and TransplantationChennai 600044India Gastroenterology and Hepatology Clinician’s PointChennai 600014Tamil NaduIndia

Post-coronavirus disease 2019(COVID-19)cholangiopathy(PCC)is a rare but lifethreatening complication of COVID-19 *** typically presents when patients recovering from the contagion and manifests as cholestasis in patients with no history of pre-existing liver *** pathogenesis of PCC is little *** injury in PCC could be mediated by the predilection of severe acute respiratory syndrome coronavirus 2 for *** PCC shows some resemblance to secondary sclerosing cholangitis in critically ill patients,it is considered as a separate and unique entity in the *** treatment options like ursodeoxycholic acid,steroids,plasmapheresis,and endoscopic retrograde cholangiopancreatography guided interventions have been tried but with limited *** have noticed significant improvement in liver function with antiplatelet therapy in a couple of *** can progress to end-stage liver disease necessitating liver *** this article,we discuss the current knowledge of PCC focusing on its pathophysiology,clinical manifestations,and management strategies.

关键词： COVID-19 liver Post-COVID-19 syndrome Long haulers Cholangiopathy Cholestasis

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Combined hepatocellular cholangiocarcinoma: A clinicopathological update

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World Journal of Hepatology 2024年第5期16卷 766-775页

作者： Mukul Vij Fadl H Veerankutty Ashwin Rammohan Mohamed Rela Department of Pathology Institute of Liver Disease and TransplantationChennai 600044India Comprehensive liver Care institute VPS LakeshoreCochin 682040India institute of liver disease and transplantation Dr.Rela Institute and Medical CentreChennai 600044India

Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling *** diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists *** diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored *** a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare *** this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.

关键词： Combined hepatocellular-cholangiocarcinoma Immunotherapy Nestin Hepatocellular carcinoma Cholangiocarcinoma liver cancer Biomarker Immune checkpoint inhibitors Pathology Genomic landscape

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Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

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Neural Regeneration Research 2025年第6期20卷 1721-1734页

作者： Xirong Xu Shoumin Xuan Shuai Chen Dan Liu Qian Xiao Jie Tu Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological diseases Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina CAS Key Laboratory of Brain Connectome and Manipulation Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Brain Connectome and Behavior the Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina University of Chinese of Academy of Sciences BeijingChina Faculty of Life and Health Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with ***, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal *** knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was ob

关键词： anxiety astrocytes basolateral amygdala behavior dihydrokainic acid excitatory amino acid transporter 2 fiber photometry glutamate LDN-212320 transporter

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Post-transplant immunosuppression and COVID-19:From a double whammy to a mixed blessing

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World Journal of transplantation 2020年第9期10卷 267-276页

作者： Ashwin Rammohan The institute of liver disease and transplantation Dr.Rela Institute and Medical CentreChennai 600044India

The coronavirus pandemic(COVID-19)has had an unprecedented effect on various disease processes and their ***-19 is likely to have a complex pathophysiological interplay with the post-transplant patients;one affecting the clinical course and outcome of the *** the absence of validated data from trials,there is strong dependence on experience based on previous similar epidemics(SARS/MERS),and from consensus based on expert *** the fact that our knowledge is rapidly evolving with time,there still is relatively limited objective data on the effect of COVID-19 on the human *** questions remain unanswered,one of which involves the management of immunosuppression in the post-transplant recipient during this *** core tenet of which continues to be that of establishing an equipoise between infection and *** review summarises the current knowledge on immune interactions of the virus,the immunomodulatory effects that may be at play,and its relation to the art of immunosuppression.

关键词： COVID-19 Post-transplant immunosuppression Immunity Review

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Overexpression of transcription factor 3 drives hepatocarcinoma development by enhancing cell proliferation via activating Wnt signaling pathway

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Hepatobiliary & Pancreatic diseases International 2022年第4期21卷 378-386页

作者： Xing-Yu Pu Dao-Feng Zheng Tao Lv Yong-Jie Zhou Jia-Yin Yang Li Jiang Department of liver Surgery and liver transplantation Center West China HospitalSichuan UniversityChengdu 610041China Laboratory of liver transplantation Frontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China

Background:Transcription factor 3(TCF3)plays pivotal roles in embryonic development,stem cell maintenance and ***,its role in hepatocellular carcinoma(HCC)remains largely *** study aimed to analyze the correlation between TCF3 expression and clinicopathological features of HCC,and further explore the underlying mechanism in HCC ***:The expression of TCF3 was collected from the Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO)HCC datasets,and further confirmed by immunostaining and Western blotting *** correlation between TCF3 expression and the clinicopathological features was *** analysis and in vitro experiments were conducted to explore the potential role of TCF3 in HCC ***:Both the mRNA and protein levels of TCF3 were significantly higher in HCC tumor tissues compared to tumor adjacent tissues(Pdisease-specific survival(P=0.022)and progression-free survival(P=0.013).Similarly,the immunostaining results revealed that the high expression of TCF3 was closely correlated with tumor size(P=0.001)and TNM stage(P=0.002),and TCF3 was an independent risk factor of *** vitro study exhibited that TCF3 knockdown dramatically suppressed cancer cell proliferation,and the underlying mechanism might be that the silencing of TCF3 reduced the expression of critical regulating proteins towards cell cycle and proteins involved in Wnt signaling ***:TCF3 expression is significantly elevated in HCC and positively associated with the tumor size and TNM stage,as well as poor prognosis of HCC *** mechanism might be that TCF3 promotes cancer cell proliferation via activating Wnt signaling pathway.

关键词： Hepatocellular carcinoma Proliferation Cell and molecular biology

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An extended treatment protocol with pegylated interferon and ribavirin for hepatitis C recurrence after liver transplantation

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World Journal of Hepatology 2011年第7期3卷 198-204页

作者： Nikroo Hashemi Victor Araya Kashif Tufail Laxmi Thummalakunta Eyob Feyssa Ashaur Azhar Mumtaz Niazi Jorge Ortiz Division of Hepatology Center for Liver Disease and TransplantationAlbert Einstein Medical Center Division of Transplant Surgery Center for Liver Disease and TransplantationAlbert Einstein Medical Center

AIM: To evaluate the efflicacy and tolerability of an extended treatment protocol and to determine the predictors of sustained virological response (SVR) after liver transplantation (LT).METHODS: Between August 2005 and November 2008, patients with recurrent hepatitis C virus (HCV) after LT were selected for treatment if liver biopsy showed at least grade 2 inflammation and/or stage 2 flibrosis. All patients were to receive pegylated interferon (PEG)/regimens combining ribavirin (RBV) for an additional 48 wk after HCV ***: Extended protocol treatment was initiated in thirty patients. Overall, 73% had end of treatmentresponse and 60% had SVR. Nineteen patients completed treatment per protocol, of them, sixteen (84%) had end of treatment response, and fourteen (74%) achieved SVR. Both early virological response and 24-week virological response were individually associated with SVR but this association was not signif icant on multivariate analysis. Eleven patients (37%) discontinued therapy due to adverse effects. Cytopenias were the most common and most severe adverse effect, and required frquent growth factor use, dose adjustments and treatment cessations. The risk of rejection was not ***: Recurrent HCV after LT can be safely treated with extended virological responseguided therpy using PEG/RBV, but requires close monitoring for treatment-related adverse effects, particularly cytopenias.

关键词： Hepatitis C virus liver transplantation Extended treatment protocol

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